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Biomolecular engineering

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Table of Contents

Overview

Definition and Scope

is a relatively new field that focuses on the manipulation and of and biomolecular processes. Its primary aim is to enhance the biocatalytic capabilities of microbes, particularly in the context of , which involves the degradation of (POPs).[1.1] This discipline encompasses the development of genetically engineered and microbes specifically designed for bioremediation purposes, thereby contributing to and pollution .[1.1]

Key Principles and Practices

Biomolecular engineering is fundamentally defined as the application of engineering principles to manipulate biomolecules and biological systems, with a strong foundation in and a focus on real-life applications. This discipline encompasses key processes such as measuring, modeling, manipulating, and creating at the biomolecular level, which are essential for the of biomolecular and systems.[2.1] Understanding the structure and function of biological molecules is crucial, as it allows for the application of principles from , , and engineering to develop new materials and molecules for diverse applications, including , , and .[3.1] A significant aspect of biomolecular engineering is the emphasis on precision, sensitivity, and selectivity in biomolecular processes. This is achieved through recognition mechanisms that rely on numerous weak but highly cooperative interactions, which facilitate exquisite control in response to various stimuli.[4.1] In the rapidly evolving field of cellular and molecular bioengineering, recent breakthroughs in areas such as , , , , and have underscored the importance of engineering biological systems.[5.1] For instance, advancements in recreating the bone marrow niche have enabled the maintenance and expansion of specific cell populations, highlighting the practical applications of biomolecular engineering in . Bioremediation represents another critical application of biomolecular engineering, particularly in addressing environmental contaminants. Emerging techniques, such as green bioremediation, are being developed to effectively tackle toxic waste in polluted environments, including a wide range of contaminants that resist biodegradation.[7.1] The engineering of genetically modified for the biodegradation of persistent organic pollutants (POPs) has become a prominent area of research, utilizing approaches like rational design and to enhance microbial capabilities.[8.1] Additionally, the integration of and into bioremediation allows for the optimization of processes by analyzing large datasets on microbial genomes and environmental conditions.[9.1] The principles of biomolecular engineering are also closely intertwined with emerging such as and synthetic biology. CRISPR-Cas9 has revolutionized , enabling precise modifications that have significant implications for health, agriculture, and biotechnology.[10.1] utilizing CRISPR for treating diseases like HIV-1 and have demonstrated the potential of this technology in therapeutic applications.[11.1] Moreover, the ability to engineer multiplexed edits using CRISPR enhances research and agricultural improvements, showcasing the versatility of biomolecular engineering in addressing complex biological challenges.[13.1] Synthetic biology, as a complementary field, holds promise for developing innovative solutions beyond laboratory settings, focusing on applications in bioproduction, biosensing, and therapeutic .[14.1] The integration of synthetic biology with biomolecular engineering principles enhances the capacity to create living systems that can respond to environmental changes and fulfill specific functions, thereby expanding the potential impact of biomolecular engineering in various domains.

History

Origins and Development

The origins of biomolecular engineering can be traced back to significant advancements in and the development of monoclonal antibodies. The concept of utilizing antibodies for disease treatment emerged in the 1890s, when Emil Adolf von Behring demonstrated that small doses of diphtheria or tetanus could confer transferable immunity between animals through serum, a discovery later attributed to the presence of antibodies.[54.1] However, it was not until the early 1960s that the structural characteristics of antibodies were elucidated, paving the way for their application in therapeutic contexts.[54.1] The formal development of monoclonal antibodies (mAbs) began with the groundbreaking work of Kohler and Milstein, who introduced murine hybridoma technology. This innovation led to the approval of Orthoclone OKT3® (muromonab-CD3) by the FDA in 1986, marking the first instance of a monoclonal antibody being utilized as a therapeutic agent.[52.1] The evolution of mAbs has since revolutionized modern medicine, with their applications expanding significantly over the years.[55.1] In parallel, the past three decades have witnessed the rise of tissue engineering and regenerative medicine, where interdisciplinary collaboration among scientists, engineers, and physicians has facilitated the creation of biological substitutes that can mimic tissues. This field aims to replace or regenerate diseased and injured tissues, further illustrating the integration of biomolecular engineering principles into practical medical applications.[43.1] The historical context of production has also played a crucial role in shaping the regulatory frameworks and measures that govern contemporary monoclonal antibody production. The successful deployment of mRNA during the has provided valuable insights into accelerating regulatory review processes and enhancing regulatory flexibility through a platform technology approach.[51.1] This experience underscores the interconnectedness of and monoclonal antibody production, highlighting the importance of historical advancements in shaping current practices in biomolecular engineering.

Milestones in Biomolecular Engineering

The field of biomolecular engineering has witnessed significant milestones over the past few decades, particularly in the areas of tissue engineering, gene editing, and cellular bioengineering. One of the most notable developments is the emergence of tissue engineering and regenerative medicine, which integrates tools from various disciplines to create biological substitutes that can mimic tissues for diagnostic and therapeutic purposes, ultimately aiming to replace or regenerate diseased or injured tissues.[41.1] In cellular and molecular bioengineering, engineering biological systems has become a rapidly growing area, driven by breakthroughs in stem cell research, tissue engineering, gene editing, synthetic biology, and biomanufacturing. For example, advancements in engineering lymphoid cells and organs, such as bone marrow and thymus tissue, have enabled the maintenance and expansion of critical cell populations, including human hematopoietic .[40.1] The development of large-scale mammalian processes has also been pivotal, particularly for the production of viral vaccines and therapeutic proteins. By 2009, a consensus process for monoclonal antibody (mAb) production was established, which included cell culture in stirred tank bioreactors followed by various purification steps.[42.1] This has facilitated the growth of the biopharmaceutical industry. In clinical applications, tissue engineering has shown promise in addressing the global disease burden. Strategies such as using polymeric scaffolds to replace lost tissues or organs have been recognized for their potential to restore normal function.[44.1] Notably, the application of autologous bone marrow (MSCs) has been demonstrated to enhance healing in various types of wounds, with studies indicating that these cells can localize to damaged areas and remain viable for extended periods.[45.1] The advent of CRISPR-Cas9 technology has revolutionized gene editing within biomolecular engineering, enabling precise modifications to the genome. This technology has been instrumental in developing therapies such as CAR-T , which involves engineering T-cells to target effectively.[47.1] Furthermore, advanced CRISPR techniques, including base editing and prime editing, have expanded the capabilities of gene editing, allowing for targeted modifications without causing double-strand breaks in DNA.[50.1]

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Recent Advancements

Emerging Technologies

Recent advancements in biomolecular engineering have led to the emergence of several innovative technologies that are transforming the field. One significant development is the discovery and utilization of biomolecular condensates, also known as membraneless organelles (MLOs), which are cellular compartments that lack a physical barrier and are composed of proteins and/or . These structures have been identified in various cellular contexts, including the nucleus and cytoplasm of eukaryotic cells. Researchers have focused on constructing synthetic biomolecular condensates that can manipulate cellular and metabolic processes with precision, revealing their roles in regulating chemical reaction rates, establishing medium-scale , and mediating subcellular .[79.1] In the realm of cellular and molecular bioengineering, there has been a notable emphasis on engineering biological systems, particularly in areas such as stem cell research, tissue engineering, and synthetic biology. Recent breakthroughs have enabled the recreation of complex biological niches, such as the bone marrow environment, which supports the maintenance and expansion of hematopoietic stem cells. This has implications for improving the efficiency of T cell differentiation and selection, as well as generating activated B cells from engineered immune organoids.[80.1] Gene editing technologies, particularly CRISPR-based systems, have emerged as transformative tools in life sciences and medicine. These technologies allow for precise modifications of material, offering new avenues for treating genetic diseases and advancing cancer therapies. For instance, CRISPR Therapeutics has initiated clinical trials for CAR T that incorporate advanced genetic edits to enhance T cell anti-cancer activity.[89.1] The rapid evolution of these technologies is accompanied by ethical considerations, particularly regarding germline editing, which raises questions about the implications of altering the genetic makeup of future generations.[92.1] Membraneless organelles (MLOs) are increasingly recognized for their role in synthetic biology, as they are formed through liquid-liquid (LLPS) and contribute to the intracellular compartmentalization of specific .[98.1] These organelles, which include structures such as stress granules, Cajal bodies, and processing bodies (P-bodies), are composed of proteins and/or nucleic acids and exhibit distinct physicochemical properties that facilitate specific enzymatic reactions.[99.1] Inspired by the organization of natural MLOs, researchers are developing synthetic systems that aim to replicate their spatiotemporal dynamics, thereby achieving programmable control over various cellular activities, including cytoskeletal organization and cell-surface signaling compartmentalization.[97.1] The design of synthetic protein condensates, also known as artificial membraneless compartments, has shown promise in regulating a wide range of cellular physiological processes, including metabolic flux control.[97.1] Overall, the integration of these emerging technologies in biomolecular engineering is poised to lead to innovative applications that could significantly impact healthcare and biological research.

Applications in Medicine and Biotechnology

Recent advancements in biomolecular engineering have led to significant applications in medicine and biotechnology, particularly through the development of innovative therapies and tools for treating genetic diseases and enhancing cellular functions. One of the most notable breakthroughs is the application of CRISPR technology, which has transformed gene editing and therapy. CRISPR-Cas systems have been effectively utilized to target various genes, demonstrating potential treatment capabilities for cancers such as lung and , as well as other genetic disorders. This technology allows for unbiased screening in , facilitating the identification of new and , and elucidating mechanisms of .[93.1] Furthermore, CRISPR has been pivotal in the creation of the world's first CRISPR-based medicine for sickle cell disease, marking a significant milestone in .[94.1] The simplicity, precision, and efficiency of CRISPR have reshaped genome engineering, driving advancements in therapies for genetic disorders, cancer, and .[95.1] In addition to CRISPR, the emergence of synthetic biomolecular condensates has opened new avenues in biotechnology. These membraneless organelles, formed through liquid-liquid phase separation, allow for the precise manipulation of cellular and metabolic processes. Engineered macromolecular assemblies, or synthetic biomolecular condensates, have been developed to regulate chemical reaction rates, establish medium-scale architectures, and mediate subcellular localization, thereby enhancing our ability to manipulate cellular behavior for therapeutic purposes.[100.1] The applications of these condensates in real-world biotechnological processes highlight their advantages over traditional , providing exquisite tools for biological manipulation.[100.1] Moreover, advancements in tissue engineering and therapeutics have also contributed significantly to medical applications. The integration of and multi-layered scaffolds has improved the of stem cells, addressing challenges related to cell survival and differentiation.[101.1] These innovations in and engineering techniques are paving the way for more effective treatments and regenerative therapies, ultimately enhancing patient care.

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Key Areas Of Research

Gene Editing and Synthetic Biology

Gene editing and synthetic biology are transformative fields within biomolecular engineering, offering innovative solutions to complex challenges in medicine and environmental sustainability. Synthetic biology merges concepts from biology, engineering, chemistry, and computer science to design organisms with novel capabilities, addressing environmental issues and advancing healthcare solutions.[114.1] By 2025, these advancements are expected to revolutionize industries such as healthcare, energy, and food production, with engineered microorganisms playing a pivotal role in generating biofuels and sustainable energy sources.[113.1] The CRISPR-Cas system stands out as a groundbreaking tool in gene editing, enabling precise genetic modifications. This technology has accelerated progress in applications like T-cell engineering for cancer therapy, where CRISPR's precision in DNA and RNA editing is crucial for developing tailored biological systems.[127.1] Despite its potential, challenges remain in clinical translation.[128.1] The interaction between engineered lymphoid cells and the microbiome is gaining attention for its impact on immune responses, with significant implications for personalized immunotherapies. The microbiome's role in immune functions, such as cytokine production and T cell response regulation, suggests it can influence immune efficacy.[120.1] Therapies that modulate the immune system, including those using engineered biomaterials, can enhance vaccine and immunotherapy safety and efficacy.[119.1] In gene editing, CRISPR-Cas9 has been instrumental in advancing CAR-T cell therapy, which involves modifying T-cells to express chimeric antigen receptors targeting tumor antigens with high specificity.[127.1] This precise editing enhances T cell functionality and persistence, promising broader disease treatment applications.[127.1] As synthetic biology evolves, it offers innovative strategies for addressing global challenges, potentially revolutionizing health and environmental sustainability.[115.1]

Tissue Engineering and Regenerative Medicine

Tissue engineering and regenerative medicine are rapidly advancing fields within cellular and molecular bioengineering (CMBE), particularly due to recent breakthroughs in various areas such as stem cell research, tissue engineering, gene editing, synthetic biology, , and biomanufacturing.[110.1] A significant focus has been placed on engineering biological systems, including the recreation of the bone marrow niche, which is essential for the maintenance and expansion of hematopoietic stem cells (HSCs).[110.1] HSCs are crucial for generating the body's blood and immune cells and reside primarily within the bone marrow microenvironment, which provides necessary signals for regulating their activities.[124.1] Recent efforts have demonstrated that recapitulating the interactions between genetically engineered stromal cells and human HSCs can enhance the long-term maintenance of lymphoid progenitors and improve the differentiation and positive selection of human T cells.[110.1] These advancements in in vitro systems not only facilitate the investigation of immune system and but also hold significant therapeutic potential for engineered stem cells.[110.1] Tissue engineering and regenerative medicine are rapidly evolving fields within cellular and molecular bioengineering (CMBE), particularly in the engineering of biological systems. Recent breakthroughs have emerged across multiple domains, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing.[110.1] A significant focus has been on recreating the bone marrow niche, which is essential for the maintenance and expansion of CD34+ cell populations.[110.1] This process involves recapitulating the interactions between genetically engineered stromal cells that express DLL1 for Notch activation and human hematopoietic stem cells (HSCs). Such advancements facilitate the long-term maintenance of lymphoid progenitors and enhance the differentiation efficiency and positive selection of human T cells.[110.1] Additionally, the development of in vitro systems that mimic the bone marrow microenvironment provides valuable opportunities for investigating the physiology and pathology of immune systems.[110.1] The development of innovative in vitro systems, such as the bone marrow-on-a-chip, has significantly advanced our ability to simulate and study the common of medical treatments, including radiotherapy and chemotherapy for cancer patients. This technology allows researchers to model how the bone marrow communicates with other organs, such as the lungs, to protect them from infections and other potential threats.[123.1] Furthermore, advancements in cell therapy, including techniques like base editing and dual antigen targeting, have improved the safety and efficacy of treatments across various cancer types. These cell-based therapies leverage the immune system's inherent ability to combat cancer and have shown promising results, particularly in the treatment of .[111.1]

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Challenges And Ethical Considerations

Ethical Issues in Biomolecular Research

The ethical implications of biomolecular engineering, particularly in gene editing and synthetic biology, have raised significant concerns regarding our moral responsibilities in genetic manipulation. Gene editing technologies, while offering potential solutions to genetic disorders and diseases, also provoke ethical questions about the extent of technological intervention in the human genome. The ability to modify genetic material introduces complexities related to the potential unintended consequences of such alterations, as well as the ethical responsibility associated with "playing the role of ".[140.1] Historically, discussions surrounding gene editing have highlighted profound . Leon Kass noted that could create new capacities and establish new norms of health and , leading to a substantial body of debating the ethical ramifications of biomedical enhancement versus therapeutic uses.[141.1] The consensus among various professional organizations and boards has generally favored a distinction between therapeutic applications, which are deemed acceptable, and enhancement uses, which are often discouraged.[141.1] The commercial introduction of genetically modified (GM) crops has initiated significant debates regarding environmental risks, which emerged soon after the development of the first transgenic organism in the 1970s. These risks can be categorized into three main areas: (1) impacts on , including effects on functions, , and non-target species; (2) concerns related to gene flow and ; and (3) the potential for the evolution of resistance in insect pests and weeds, particularly in relation to Bacillus thuringiensis (Bt) crops.[137.1] Additionally, the increasing persistence of hazardous contaminants in the environment has led to a rise in the use of bioremediation techniques, which often involve genetically engineered microbes (GEMs). These microbes are developed through biotechnology to enhance specific traits by introducing stronger proteins into , thereby addressing environmental contamination challenges.[139.1] As the field of biomolecular engineering continues to evolve, there is a pressing need to improve ethical frameworks to address these rapid advancements. This includes establishing guidelines that not only consider the potential benefits of gene editing and synthetic biology but also the ethical implications and long-term consequences of such technologies.[140.1] The ongoing discourse emphasizes the importance of balancing innovation with ethical responsibility, ensuring that advancements in biomolecular engineering are pursued with caution and .

Regulatory and Safety Concerns

Regulatory frameworks play a crucial role in addressing the ecological risks associated with biomolecular engineering projects. is essential for evaluating the likelihood of environmental impacts resulting from exposure to chemicals and other stressors, thereby informing regulatory decisions that prioritize .[150.1] Concerns have been raised by ecologists regarding the potential impacts of releasing genetically engineered organisms (GEOs) into the environment, highlighting the need for robust regulatory measures that innovation with ecological safety.[151.1] The rise in environmental contamination has led to an increased reliance on bioremediation techniques, including the development of genetically engineered microbes (GEMs) designed to enhance specific traits for environmental cleanup.[152.1] However, the regulatory landscape for genetic engineering remains complex and evolving. In regions such as Africa, regulatory frameworks are still developing, and there are significant challenges in addressing the potential misuse of genetic engineering technologies.[158.1] In the United States, the regulation of (GMOs) is fragmented, with oversight divided among various agencies, including the FDA, EPA, and USDA, depending on the intended use of the GM product.[159.1] This lack of a cohesive federal framework can complicate the regulatory process and may hinder innovation. Furthermore, ethical dilemmas arise at various stages of biomolecular engineering, particularly concerning human subjects, , and equitable access to therapies derived from biomaterials.[161.1] Internationally, inappropriate and politicized have limited the benefits of , with agreements such as the Cartagena Protocol on Biosafety posing barriers to innovation, particularly in food-insecure countries.[162.1] The Coordinated Framework for the Regulation of Biotechnology established in 1986 outlines how U.S. agencies collaborate to regulate GMOs, ensuring that these products meet safety standards comparable to non-GMO foods.[163.1] However, the emergence of synthetic biology presents new regulatory challenges, as existing frameworks may not adequately address the complexities of organisms that can evolve and multiply within the body.[164.1]

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Future Directions

Innovations in Biomolecular Engineering

Innovations in biomolecular engineering are rapidly evolving, driven by advancements across various scientific disciplines. One significant area of focus is the development of hybrid biochemical and chemical conversion bioprocesses, which aim to enhance biological conversion processes through innovative paradigms such as microbial consortia and cell-free systems. This approach is complemented by efforts in bioprocess development tailored for , which leverages data-driven machine learning techniques to accelerate design and engineering processes that exploit new biological insights.[167.1] Recent breakthroughs have also highlighted the role of biomolecular condensates, or membraneless organelles (MLOs), in cellular function. These structures, composed of proteins and nucleic acids, facilitate the compartmentalization and regulation of biochemical activities within cells. Research has increasingly focused on constructing synthetic biomolecular condensates that serve as precise tools for manipulating cellular and metabolic processes, revealing their potential to regulate chemical reaction rates and influence subcellular localization.[175.1] In the realm of cellular and molecular bioengineering, significant strides have been made in stem cell research and tissue engineering. For example, the engineering of lymphoid cells and organs, such as bone marrow and thymus tissue, has shown promise in maintaining and expanding hematopoietic stem cell populations. This includes recreating the bone marrow niche to enhance the differentiation and selection of human T cells, thereby providing new avenues for investigating immune system physiology and pathology.[169.1] The integration of machine learning (ML) with experimental techniques in biomolecular engineering has significantly advanced the analysis of complex datasets generated by high-throughput technologies. As computational power has increased, researchers have transitioned to data-driven methods that utilize ML algorithms to deduce rules directly from data, enabling efficient and comprehensive analysis of large and complex datasets.[172.1] Among these advancements, algorithms based on U-Net have been developed to enhance the signal-to- ratio (SNR) in stimulated Raman scattering (SRS) imaging. With minor optimizations to the U-Net , (CNNs) have been applied to denoise SRS data, thereby improving the quality of biological images under low SNR conditions, such as low power.[172.1] Additionally, cell segmentation and classification based on the metabolic signatures of individual cells obtained from hyperspectral SRS images have been successfully achieved through an SVM-based machine learning pipeline, validating this approach for high-throughput, semi-automatic analysis in both basic research and clinical applications.[172.1] However, challenges persist in ensuring that these data-driven models accurately reflect biological realities, necessitating ongoing research and refinement in this field.[172.1] Despite these advancements, challenges persist, particularly in replicating the complex microenvironment of the bone marrow for effective stem cell therapies. The intricate interactions within the bone marrow niche, which include various cell types that regulate hematopoietic stem cells, pose significant hurdles for engineering efforts aimed at developing reliable .[178.1] Addressing these challenges will be crucial for the future success of stem cell therapies and the broader field of biomolecular engineering.

References

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sciencedirect

https://www.sciencedirect.com/topics/engineering/biomolecular-engineering

[1] Biomolecular Engineering - an overview | ScienceDirect Topics 6.1 Genetically modified microbes. The main aim of biomolecular engineering in the field of bioremediation is to enhance the biocatalytic capability of microbes to degrade POPs. It is a relatively new field that exploits engineering biomolecules and biomolecular processes for development of genetically engineered enzymes or microbes for bioremediation purpose (Ang et al., 2005).

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quizlet

https://quizlet.com/study-guides/introduction-to-biomolecular-engineering-30fb79df-8346-40bf-94ae-afc34228a098

[2] Introduction to Biomolecular Engineering Study Guide - Quizlet Introduction to Biomolecular Engineering Definition and Scope. Definition: Biomolecular engineering applies engineering principles to manipulate biomolecules and systems. Foundation: It is rooted in molecular biology, focusing on real-life applications. Key Processes: Involves measuring, modeling, manipulating, and making at the biomolecular level.

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mit

https://be.mit.edu/research/biomolecular-design/

[3] Biomolecular Design | MIT Department of Biological Engineering The design of biomolecular and biomaterial systems involves understanding the structure and function of biological molecules and systems, as well as applying principles of chemistry, physics, and engineering to create new materials and molecules that can be used in a variety of applications, such as medicine, biotechnology, and materials science.

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nih

https://www.ncbi.nlm.nih.gov/books/NBK214486/

[4] Understanding Biomolecular Processes: Toward Principles That Govern ... The focus of the chapter is on learning the principles of biomolecular processes, which could then be used to design biomolecular materials. ... The key process that facilitates this precision, sensitivity, and selectivity, and the exquisite control in response, is recognition based on the many weak but highly cooperative interactions that are

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8147909/

[5] Recent Advances in Cellular and Molecular Bioengineering for Building ... In the field of cellular and molecular bioengineering (CMBE), engineering biological systems is one of the fastest-growing areas, especially with recent research breakthroughs simultaneously in multiple fields, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing. Efforts have also been focused on engineering lymphoid cells and organs, including bone marrow, thymus tissue, and lymph nodes.49 For instance, recreating the bone marrow niche allows for the maintenance and expansion of the CD34+ cell population.28,65 Recapitulating the interaction of stromal cells (genetically engineered to express DLL1 for Notch activation) and human hematopoietic stem cells (HSCs) enables the long-term maintenance of lymphoid progenitors and improves the efficiency of differentiation and positive selection of human T cells.93 Activated B cells can be produced from engineered immune organoids mimicking the germinal center.2,67,74,80 The development of these in vitro systems provides an opportunity for investigating the physiology and pathology of immune systems and for

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acs

https://pubs.acs.org/doi/10.1021/bk-2024-1476.ch001

[7] Bioremediation of Emerging Contaminants in Water. Volume 2 Green bioremediation is an innovative and rapidly expanding technique that holds great promise for tackling the issue of toxic waste in polluted environments. Our planet is burdened with a wide array of contaminants, ranging from heavy metals and polychlorinated biphenyls to plastics and agrochemicals. These pollutants persist in the environment due to their resistance to biodegradation

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0141022905001262

[8] Recent advances in the bioremediation of persistent organic pollutants ... With recent advances in biomolecular engineering, the bioremediation of persistent organic pollutants (POPs) using genetically modified microorganisms has become a rapidly growing area of research for environmental protection. Two main biomolecular approaches, rational design and directed evolution, have been developed to engineer enhanced microorganisms and enzymes for the biodegradation of

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S2949750724000622

[9] A comprehensive review of sustainable bioremediation techniques: Eco ... Further studies have explored the role of bioinformatics and machine learning in predicting and optimizing bioremediation processes. By analyzing large datasets on microbial genomes and environmental conditions, researchers can identify key factors that influence bioremediation efficacy and tailor interventions more precisely.

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S1773224724000066

[10] Principles of CRISPR-Cas9 technology: Advancements in genome editing ... Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery - ScienceDirect Review article Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery open access The rapid advancement of CRISPR-Cas9 technology has instigated a profound transformation in genome editing with significant implications for fields like health, agriculture, and biotechnology. It emphasizes CRISPR-Cas9's preeminence in the domain of precise genome editing, driving breakthroughs in personalized medicine, gene therapy, and agriculture. CRISPR-Cas9 stands on the brink of unlocking new possibilities in genome editing, providing innovative solutions to address pressing global challenges. Previous article in issue Next article in issue Recommended articles No articles found. For all open access content, the relevant licensing terms apply.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8819410/

[11] Basic Principles and Clinical Applications of CRISPR-Based Genome ... The first clinical trial on CRISPR-based ex vivo genome editing attempted to treat human immunodeficiency virus type 1 (HIV-1) infection.30 Disruption of the CCR5 gene, which encodes an important co-receptor for viral entry, was induced by nucleofection of ribonucleoprotein complexes targeting CCR5 into patient-derived hematopoietic stem and progenitor cells (HSPCs), which were subsequently transferred back to the patient. Recently, a clinical trial attempting to treat severe monogenetic diseases with CRISPR-based genome editing reported promising results.31 Sickle cell disease and beta-thalassemia represent distinct groups of inherited hemoglobinopathies caused by mutations in the hemoglobin beta-subunit (HBB) gene, which lead to mutant, reduced, or absent beta-globin proteins.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC10916045/

[13] Application of CRISPR-Cas9 genome editing technology in various fields ... For instance, in a study by Hsu et al., CRISPR-Cas9 was used to successfully edit multiple genes simultaneously, providing a powerful tool for functional genomics research . An example of its application in crop improvement can be seen in the work of Li et al., where CRISPR-Cas9 was used to enhance rice grain yield by targeting a gene involved in grain size regulation . In a study by Li et al., CRISPR-Cas9 was utilized to enhance rice grain yield by precisely editing genes associated with grain size regulation . While the specific references on CRISPR-Cas9 technology in nanotechnology are limited, some researchers published articles and reviews on CRISPR-based delivery systems, nanocarriers for gene editing, or nanotechnology-enabled gene regulation for further insights into the potential synergies between CRISPR-Cas9 technology and nanotechnology .

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nature

https://www.nature.com/articles/s41467-021-21740-0

[14] Applications, challenges, and needs for employing synthetic biology ... Advertisement View all journals Search Log in Explore content About the journal Publish with us Sign up for alerts RSS feed nature nature communications perspectives article Applications, challenges, and needs for employing synthetic biology beyond the lab Download PDF Download PDF Perspective Open access Published: 02 March 2021 Applications, challenges, and needs for employing synthetic biology beyond the lab Sierra M. Brooks ORCID: orcid.org/0000-0002-6914-25041 & Hal S. Alper ORCID: orcid.org/0000-0002-8246-86051,2 Nature Communications volume 12, Article number: 1390 (2021) Cite this article 51k Accesses 62 Altmetric Metrics details Subjects Biotechnology Synthetic biology Abstract Synthetic biology holds great promise for addressing global needs. However, most current developments are not immediately translatable to ‘outside-the-lab’ scenarios that differ from controlled laboratory settings. Here we analyze recent advances in developing synthetic biological platforms for outside-the-lab scenarios with a focus on three major application spaces: bioproduction, biosensing, and closed-loop therapeutic and probiotic delivery. We focus this Perspective on three major application spaces for the outside-the-lab deployment of synthetic biology: bioproduction, biosensing, and closed-loop living therapeutic and probiotic delivery.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8147909/

[40] Recent Advances in Cellular and Molecular Bioengineering for Building ... In the field of cellular and molecular bioengineering (CMBE), engineering biological systems is one of the fastest-growing areas, especially with recent research breakthroughs simultaneously in multiple fields, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing. Efforts have also been focused on engineering lymphoid cells and organs, including bone marrow, thymus tissue, and lymph nodes.49 For instance, recreating the bone marrow niche allows for the maintenance and expansion of the CD34+ cell population.28,65 Recapitulating the interaction of stromal cells (genetically engineered to express DLL1 for Notch activation) and human hematopoietic stem cells (HSCs) enables the long-term maintenance of lymphoid progenitors and improves the efficiency of differentiation and positive selection of human T cells.93 Activated B cells can be produced from engineered immune organoids mimicking the germinal center.2,67,74,80 The development of these in vitro systems provides an opportunity for investigating the physiology and pathology of immune systems and for

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annualreviews

https://www.annualreviews.org/content/journals/10.1146/annurev-chembioeng-061010-114257

[41] Tissue Engineering and Regenerative Medicine: History, Progress, and ... The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this

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nsf

https://par.nsf.gov/servlets/purl/10424485

[42] Biopharmaceutical Manufacturing: Historical ... - NSF Public Access Much of the foundational work for large-scale mammalian cell culture processes using both adherent and suspension cell lines was done for the non-recombinant production of viral vaccines for livestock, human interferons, or antibiotics, and principles from these industries were applied to the cell culture bioreactors used by the early biopharma industry ( 30 –32 ). Narrowing the range of operating conditions helped to limit the scope of experimentation needed to define a purification process with acceptable yields and purity levels for a new mAb. By 2009, many companies converged on a consensus mAb production process: cell culture in a stirred tank production bioreactor followed by harvest, Protein A affinity chromatography, viral inactivation (VI), one or two IEX chromatography steps (anion and/or cation exchange), virus filtration, and tangential-flow ultrafiltration (TFUF) to produce drug substance ( 77 , 91 , 92 ).

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nih

https://pubmed.ncbi.nlm.nih.gov/22432625/

[43] Tissue engineering and regenerative medicine: history ... - PubMed The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues.

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nih

https://pubmed.ncbi.nlm.nih.gov/21154670/

[44] Tissue engineering for clinical applications - PubMed Tissue engineering is increasingly being recognized as a beneficial means for lessening the global disease burden. One strategy of tissue engineering is to replace lost tissues or organs with polymeric scaffolds that contain specialized populations of living cells, with the goal of regenerating tissues to restore normal function.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC10290827/

[45] Current and Future Perspectives on Skin Tissue Engineering: Key ... In the mid-2000s, several groups showed that healing in various types of cutaneous wounds (e.g., excisional, burn, radiation damage) could be accelerated and improved with application of autologous bone marrow MSCs.[110-112] These prohealing effects may even persist over significant periods of time—studies have shown that, when introduced systemically, exogenous MSCs can localize in damaged areas and maintain viability for up to 6 years after implantation in humans. However, the responsiveness of MSCs to immune signaling is mostly localized to their microenvironment, requiring either induction of endogenous MSCs migration, or direct placement of exogenous cells at the site to maximize therapeutic benefits. Many hydrogel and polymer scaffolds have been thus been developed to induce activity and maintain MSC viability to promote the production of angiogenic, immunomodulatory, matrix remodeling, or other regenerative cytokines. In skin tissue engineering in particular, MSCs can function to promote wound healing when immobilized in hydrogels placed over the wound site or when added as an intermediary layer in split-thickness skin graft procedures.

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11669675/

[47] Advances in CRISPR-Cas technology and its applications: revolutionising ... | Blood | Hemophilia B | F9 | Corrected F9 gene in iPSCs using CRISPR-Cas9; restored F9 expression in hepatocyte-like cells | Morishige et al. One prominent application of CRISPR-Cas9 technology is its application in engineering T-cells express CARs. CAR-T cell therapy is a genetically modified T-cell that expresses CARs, targeting tumour-associated antigens (TAAs) or tumour-specific antigens (TSAs) with high specificity, thereby targeting and eliminating cancer cells (Jogalekar et al., 2022). CRISPR-Cas9 technology has enhanced CAR-T therapy by enabling precise genetic edits that improve T cell functionality, persistence, and specificity (Dimitri et al., 2022). CRISPR-Cas gene editing is utilised to introduce oncolytic viruses with therapeutic genes, enhancing their cancer tissue selectivity and suppressing antiviral protective mechanisms employed by malignant cells (Wang et al., 2022b).

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC11057861/

[50] CRISPR Advancements for Human Health - PMC - PubMed Central (PMC) Advanced CRISPR approaches such as base editing and prime editing use modified Cas enzymes which can induce precise single nucleotide changes in the genome without creating double-strand DNA breaks.2 CRISPR can also be used to activate genes (CRISPRa) or inactivate genes (CRISPRi) by targeting modified sgRNA/Cas complexes to the gene’s promoter region, recruiting transcription factors for increased gene expression or repressors for decreasing gene expression.3 In addition to engineering patient’s own T-cells (autologous T-cells), there is increasing interest in using T-cells from healthy donors (allogeneic T-cells) as an off-the-shelf cell therapy product.42 Gene-edited allogeneic T-cells, with mechanisms to reduce graft-vs-host rejection, have shown promise as a strategy to broaden access to engineered T-cell therapies.43 Recent studies have demonstrated the feasibility of disrupting genes such as PD-1 and TCR using CRISPR-Cas9 in allogeneic T-cells before adoptive transfer into patients.44,45 Allogeneic CRISPR-edited T-cell therapies are now being evaluated in early-phase clinical trials, with the goals of maintaining anti-tumor potency while minimizing the risk of graft-vs-host disease.46

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mdpi

https://www.mdpi.com/2076-393X/12/5/528

[51] The Platform Technology Approach to mRNA Product Development and Regulation mRNA vaccines have been instrumental in significantly reducing global mortality and morbidity from SARS-CoV-2 infection [].With the successful administration of mRNA vaccines to billions of people, much has been learned about safely accelerating regulatory review and approval processes for subsequent iterations of the initial vaccine and regulatory flexibility using a platform technology approach.

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allucent

https://www.allucent.com/resources/blog/monoclonal-antibodies-past-present-and-future

[52] Monoclonal Antibodies: What They Are, FDA History & Future - Allucent To understand antibody humanization, it is helpful to review a brief history of monoclonal antibodies. The Origin of Monoclonal Antibodies. In 1986, Orthoclone OKT3® (muromonab-CD3) became the first monoclonal antibody approved by the FDA. Its production was based on the Nobel-winning work of Kohler and Milstein on murine hybridoma technology.

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ahajournals

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.113.002033

[54] Evolution and Emergence of Therapeutic Monoclonal Antibodies: The concept of using antibodies for the treatment of disease dates back to the 1890s, when Emil Adolf von Behring discovered the ability of small doses of diphtheria or tetanus toxin to produce transferable immunity between animals via serum 1 (later attributed to the presence of antibodies). However, it was not until the early 1960s that structural characteristics of antibodies were described

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC11231668/

[55] A Comprehensive Review of Monoclonal Antibodies in Modern Medicine ... Abstract. Monoclonal antibodies (mAbs) have emerged as potent therapeutic agents, revolutionizing the landscape of modern medicine. This comprehensive review traces the evolution of mAbs from their inception to their current prominence, highlighting key milestones in their development and exploring their diverse therapeutic applications.

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0734975024001460

[79] Recent advances in engineering synthetic biomolecular condensates Over the past decade, numerous cellular compartments lacking a physical barrier, also referred to as biomolecular condensates or membraneless organelles (MLOs), composed of proteins and/or nucleic acids have been uncovered in the nucleus and cytoplasm, or on the membranes of eukaryotic cells (Lyon et al., 2021). To date, a great deal of attention has been paid to using natural or artificial proteins, and occasionally nucleic acids, for the construction of engineered macromolecular assemblies, i.e., synthetic biomolecular condensates or artificial MLOs, which generate exquisite biological tools for precisely manipulating cellular and metabolic processes in living cells. Corresponding theoretical and experimental results have uncovered the functions of protein condensates at different scales, such as regulating chemical reaction rates (molecular level), establishing medium-scale architectures (mesoscale level), and mediating subcellular localization (cellular level) (Lyon et al., 2021).

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8147909/

[80] Recent Advances in Cellular and Molecular Bioengineering for Building ... In the field of cellular and molecular bioengineering (CMBE), engineering biological systems is one of the fastest-growing areas, especially with recent research breakthroughs simultaneously in multiple fields, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing. Efforts have also been focused on engineering lymphoid cells and organs, including bone marrow, thymus tissue, and lymph nodes.49 For instance, recreating the bone marrow niche allows for the maintenance and expansion of the CD34+ cell population.28,65 Recapitulating the interaction of stromal cells (genetically engineered to express DLL1 for Notch activation) and human hematopoietic stem cells (HSCs) enables the long-term maintenance of lymphoid progenitors and improves the efficiency of differentiation and positive selection of human T cells.93 Activated B cells can be produced from engineered immune organoids mimicking the germinal center.2,67,74,80 The development of these in vitro systems provides an opportunity for investigating the physiology and pathology of immune systems and for

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https://www.endocrinologyadvisor.com/features/future-of-crispr/

[89] Future of CRISPR: Gene Editing Technologies Herald Landmark Clinical Trials In the acute and critical care arena, advancements in gene editing for cancer have been among the most important gene editing applications.22 Following positive early-phase outcomes and improved manufacturing techniques that enhance CAR T cell yields, CRISPR Therapeutics has progressed to phase 1/2 trials (ClinicalTrials.gov Identifiers: NCT05643742, NCT05795595) with their advanced CAR T cell therapies targeting CD70 and CD19 proteins, which are prevalent on various tumor and blood cancer cells.23 These updated therapies now feature additional edits to Regnase-1 and TGFBR-2 genes to enhance T cell anti-cancer activity by deactivating genes that inhibit T cell functions.

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genome

https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns

[92] What are the Ethical Concerns of Genome Editing? Most of the ethical discussions related to genome editing center around human germline because editing changes made in the germline would be passed down to future generations. Overview The debate about genome editing is not a new one but has regained attention following the discovery that CRISPR has the potential to make such editing more accurate and even "easy" in comparison to older technologies. As of 2014, there were about 40 countries that discouraged or banned research on germline editing, including 15 nations in Western Europe, because of ethical and safety concerns.3 There is also an international effort led by the US, UK, and China to harmonize regulation of the application of genome editing technologies. Researchers and ethicists who have written and spoken about genome editing, such as those present at the International Summit on Human Gene Editing, generally agree that until germline genome editing is deemed safe through research, it should not be used for clinical reproductive purposes; the risk cannot be justified by the potential benefit. Researchers and bioethicists also worry about the possibility of obtaining truly informed consent from prospective parents as long as the risks of germline therapy are unknown.10 Justice and Equity As with many new technologies, there is concern that genome editing will only be accessible to the wealthy and will increase existing disparities in access to health care and other interventions.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8444435/

[93] Applications and challenges of CRISPR-Cas gene-editing to disease ... A variety of studies have applied CRISPR-Cas systems for effectively targeting different genes and have managed to prove the potential treatment ability for initiation or progression of lung cancer,64 breast cancer,65,66 and many other types of cancers.67–69 Meanwhile, the CRISPR-Cas system has been harnessed to serve as a powerful tool with the ability of unbiased screening of precision medicine including identification of new drug targets, biomarkers, and elucidation of mechanisms leading to drug resistance.70–72 In short, there are tremendous potential applications for CRISPR-Cas and their derivative systems (i.e. dCas9) due to the ability to accurately determine the underlying disease causes, genetic mutation variants, immunological regulatory factors, cell signaling mediators, and drug targets as well as drug molecules and therapeutics.

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harvard

https://hms.harvard.edu/news/creating-worlds-first-crispr-medicine-sickle-cell-disease

[94] Creating the World's First CRISPR Medicine, for Sickle Cell Disease Creating the World’s First CRISPR Medicine, for Sickle Cell Disease | Harvard Medical School When Vijay Sankaran was an MD-PhD student at Harvard Medical School in the mid-2000s, one of his first clinical encounters was with a 24-year-old patient whose sickle cell disease left them with almost weekly pain episodes. In 2008, Orkin, Sankaran, and colleagues achieved their vision by identifying a new therapeutic target for sickle cell disease. The decision has ushered in a new era for sickle cell disease treatment — and marked the world’s first approval of a medicine based on CRISPR/Cas9 gene-editing technology. Plus, researchers including Orkin, Sankaran, and those at Vertex continue to conduct research to make sickle cell treatment more effective, more efficient, and appropriate for even more patients.

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frontiersin

https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1517298/full

[95] Editorial: CRISPR: the game changer in gene and cell therapy Frontiers | Editorial: CRISPR: the game changer in gene and cell therapy 4 Exploring research frontiers in CRISPR-based therapies This article is part of the Research Topic CRISPR: The Game Changer in Gene and Cell Therapy View all 6 articles CRISPR’s simplicity, precision, and efficiency have reshaped genome engineering, driving the development of innovative therapies for genetic disorders, cancer, and infectious diseases. This editorial highlights the latest advancements in CRISPR technology, discussing its applications and the ongoing challenges in gene and cell therapy, with insights from recent research under the topic CRISPR—The Game Changer. 4 Exploring research frontiers in CRISPR-based therapies CRISPR technology has ushered in a new era of gene and cell therapy, offering unprecedented precision and potential for treating genetic disorders, cancer, and infectious diseases.

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https://www.sciencedirect.com/science/article/pii/S0734975024000491

[97] Recent advances in design and application of synthetic membraneless ... Evidence is now mounting that membraneless organelles, such as stress granules, P bodies, and Cajal bodies, are initially formed through liquid-liquid phase separation (LLPS) or condensation (Alberti et al., 2019; Banani et al., 2017; Boeynaems et al., 2018; Shin and Brangwynne, 2017). Inspired by the intricate yet well-organized processes evident in natural MLOs, scientists have endeavored to develop synthetic systems that can mimic the spatiotemporal organization observed in their natural counterparts, and furthermore achieve the programmable control of specific cellular activities, such as cytoskeletal organization and cell-surface signaling compartmentalization (Garabedian et al., 2021; Li et al., 2022a). Notably, numerous synthetic protein condensates, also referred to as artificial membraneless compartments, have been deliberately designed and utilized to regulate a wide range of cellular physiological processes, including metabolic flux control,

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nih

https://pubmed.ncbi.nlm.nih.gov/36424481/

[98] A guide to membraneless organelles and their various roles in gene ... Membraneless organelles (MLOs) are detected in cells as dots of mesoscopic size. By undergoing phase separation into a liquid-like or gel-like phase, MLOs contribute to intracellular compartmentalization of specific biological functions. In eukaryotes, dozens of MLOs have been identified, including …

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wiley

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cplu.202400483

[99] Artificial Compartments Encapsulating Enzymatic Reactions: Towards the ... Many membraneless organelles, such as stress granules, cajal body, and processing bodies (P-bodies), are phase-separated biomolecular condensates of proteins and/or nucleic acids (Figure 3A). 26 These membraneless compartments exhibit distinct physicochemical properties and would help to carry out the specific enzymatic reactions. 27

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0734975024001460

[100] Recent advances in engineering synthetic biomolecular condensates Over the past decade, numerous cellular compartments lacking a physical barrier, also referred to as biomolecular condensates or membraneless organelles (MLOs), composed of proteins and/or nucleic acids have been uncovered in the nucleus and cytoplasm, or on the membranes of eukaryotic cells (Lyon et al., 2021). To date, a great deal of attention has been paid to using natural or artificial proteins, and occasionally nucleic acids, for the construction of engineered macromolecular assemblies, i.e., synthetic biomolecular condensates or artificial MLOs, which generate exquisite biological tools for precisely manipulating cellular and metabolic processes in living cells. Corresponding theoretical and experimental results have uncovered the functions of protein condensates at different scales, such as regulating chemical reaction rates (molecular level), establishing medium-scale architectures (mesoscale level), and mediating subcellular localization (cellular level) (Lyon et al., 2021).

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biomedcentral

https://biomaterialsres.biomedcentral.com/articles/10.1186/s40824-018-0148-4

[101] Recent advances in stem cell therapeutics and tissue engineering ... Recent advances in stem cell therapeutics and tissue engineering strategies | Biomaterials Research | Full Text In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases. Although stem cell therapy provides a new paradigm in tissue regeneration, they have limitation in clinical application due to poor survival and differentiation potentials of the transplanted cells . Therefore, multi-layered 3D scaffolds are needed for construction of engineered tissues using stem cells. 3D bioprinting of stem cells In this paper, we reviewed the current status of stem cell technologies, biomedical engineering, and nanotechnology for tissue regeneration. Biomaterials and stem cells for tissue engineering.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8147909/

[110] Recent Advances in Cellular and Molecular Bioengineering for Building ... In the field of cellular and molecular bioengineering (CMBE), engineering biological systems is one of the fastest-growing areas, especially with recent research breakthroughs simultaneously in multiple fields, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing. Efforts have also been focused on engineering lymphoid cells and organs, including bone marrow, thymus tissue, and lymph nodes.49 For instance, recreating the bone marrow niche allows for the maintenance and expansion of the CD34+ cell population.28,65 Recapitulating the interaction of stromal cells (genetically engineered to express DLL1 for Notch activation) and human hematopoietic stem cells (HSCs) enables the long-term maintenance of lymphoid progenitors and improves the efficiency of differentiation and positive selection of human T cells.93 Activated B cells can be produced from engineered immune organoids mimicking the germinal center.2,67,74,80 The development of these in vitro systems provides an opportunity for investigating the physiology and pathology of immune systems and for

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https://www.sciencedirect.com/science/article/pii/S0165614724002268

[111] Advances in cell therapy: progress and challenges in hematological and ... Advances in cell therapy: progress and challenges in hematological and solid tumors - ScienceDirect Advances in cell therapy: progress and challenges in hematological and solid tumors Cell engineering advancements, including base editing and dual antigen targeting, improve safety and efficacy across cancer types. Cell-based therapies harness the endogenous ability of the immune system to fight cancer and have shown promising results in the treatment of hematological malignancies. In this review, we examine the challenges and future directions of the most prominent cell-based therapies, including chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes (TILs), and natural killer (NK) cells, and emerging modalities. No articles found. For all open access content, the Creative Commons licensing terms apply.

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https://widexplore.com/synthetic-biology-in-2025-how-it-will-revolutionize-healthcare-and-sustainability/

[113] Synthetic Biology in 2025: Revolutionizing Healthcare, Agriculture, and ... What to Expect by 2025: By 2025, synthetic biology will be at the forefront of cutting-edge research, and advancements in genetic engineering will lead to real-world applications that can have a major impact on industries like healthcare, energy, and food production. Synthetic biology has the potential to make clean energy more efficient by engineering microorganisms to produce biofuels, hydrogen, and other sustainable energy sources. Governments and international organizations will create policies that ensure the safe and responsible development of synthetic biology applications, particularly in sensitive areas like healthcare and environmental remediation. By 2025, synthetic biology will have established itself as a transformative field with the potential to revolutionize industries like healthcare, agriculture, environmental sustainability, and clean energy.

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0734975023001465

[114] Synthetic biology tools for environmental protection Synthetic biology is the application of engineering, science, and technology to edit the genetic material of living organisms in order to enable them to perform new functions (Cameron et al., 2014).Such engineered organisms can provide robust solutions to our current environmental challenges.

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thermofisher

https://www.thermofisher.com/blog/life-in-the-lab/5-synthetic-biology-discoveries-accelerating-global-sustainability/

[115] 5 Synthetic Biology Discoveries Accelerating Global Sustainability 5 Synthetic Biology Discoveries Accelerating Global Sustainability - Life in the Lab Accelerating ScienceLife in the Lab / General / 5 Synthetic Biology Discoveries Accelerating Global Sustainability From the production of rocket biofuel to bioremediation of pollutants, innovations in the field of synthetic biology may seem straight out of science fiction. 1. Bacteria, yeast, and rockets: synthetic biology and biofuel innovation 2. Plants to the rescue: synthetic biology, carbon capture, and GMO trees 4. Decarbonizing chemical production: harnessing synthetic biology for more sustainable manufacturing With wide-scale, organized application and collaborative engineering between policy makers, scientists, and industry leaders, synthetic biology offers considerable potential to achieve lasting sustainability without disrupting modern industry, enabling a cleaner, safer future for this planet, and everyone on it.

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nature

https://www.nature.com/articles/s44222-022-00016-2

[119] Targeted modulation of immune cells and tissues using engineered ... Advertisement View all journals Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews bioengineering review articles article Review Article Published: 30 January 2023 Targeted modulation of immune cells and tissues using engineered biomaterials Parisa Yousefpour1, Kaiyuan Ni1 & Darrell J. Irvine1,2,3,4,5 Nature Reviews Bioengineering volume 1, pages 107–124 (2023)Cite this article 26k Accesses 77 Citations 42 Altmetric Metrics details Subjects Immunology Translational research Abstract Therapies modulating the immune system offer the prospect of treating a wide range of conditions including infectious diseases, cancer and autoimmunity. Biomaterials can promote specific targeting of immune cell subsets in peripheral or lymphoid tissues and modulate the dosage, timing and location of stimulation, thereby improving the safety and efficacy of vaccines and immunotherapies. Here, we review recent advances in biomaterials-based strategies, focusing on targeting of lymphoid tissues, circulating leukocytes, tissue-resident immune cells and immune cells at disease sites. These approaches can improve the potency and efficacy of immunotherapies by promoting immunity or tolerance against different diseases.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC7362776/

[120] Impact of the Microbiome on the Immune System - PMC Short-chain fatty acids, like butyrate, are a common product of gut microbiota which potentially enhance the antipathogenic function of CD8+ T cells via up-regulation of IFN-γ.53 CD4+ T cells are helper cells that regulate immune responses through the release of cytokines and activation of other immune components. Microbiota have been linked to multiple immune functions, including the production of cytokines, maintenance of homeostasis, T cell production, and regulation of the immune system.75–77 The microbiome is involved in heavy interplay with the immune system and is affected to a great degree by environmental factors through birth and infancy.78 It has also been identified as a potential player in the development of certain immune system components such as myeloid cell derivatives,79 suggesting that the microbiota have various roles in the differentiation and efficacy of immune responses.

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upenn

https://penntoday.upenn.edu/news/penn-engineering-medicine-borrowing-natures-blueprint-how-scientists-replicated-bone-marrow

[123] Borrowing nature's blueprint: How scientists replicated bone marrow The bone marrow-on-a-chip allows researchers to simulate and study common side effects of medical treatments, such as radiotherapy and chemotherapy for cancer patients. When connected to another device, it can even model how the bone marrow communicates with other organs, like the lungs, to protect them from infections and other potentially

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nih

https://pubmed.ncbi.nlm.nih.gov/35580474/

[124] Current insights into the bone marrow niche: From biology in vivo to ... Hematopoietic stem cells (HSCs) are fundamental to the generation of the body's blood and immune cells. They reside primarily within the bone marrow (BM) niche microenvironment, which provides signals responsible for the regulation of HSC activities. While our understanding of these signalling mecha …

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC11669675/

[127] Advances in CRISPR-Cas technology and its applications: revolutionising ... | Blood | Hemophilia B | F9 | Corrected F9 gene in iPSCs using CRISPR-Cas9; restored F9 expression in hepatocyte-like cells | Morishige et al. One prominent application of CRISPR-Cas9 technology is its application in engineering T-cells express CARs. CAR-T cell therapy is a genetically modified T-cell that expresses CARs, targeting tumour-associated antigens (TAAs) or tumour-specific antigens (TSAs) with high specificity, thereby targeting and eliminating cancer cells (Jogalekar et al., 2022). CRISPR-Cas9 technology has enhanced CAR-T therapy by enabling precise genetic edits that improve T cell functionality, persistence, and specificity (Dimitri et al., 2022). CRISPR-Cas gene editing is utilised to introduce oncolytic viruses with therapeutic genes, enhancing their cancer tissue selectivity and suppressing antiviral protective mechanisms employed by malignant cells (Wang et al., 2022b).

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acs

https://pubs.acs.org/doi/10.1021/acssynbio.4c00686

[128] Engineering a New Generation of Gene Editors: Integrating Synthetic ... CRISPR-Cas technology has revolutionized biology by enabling precise DNA and RNA edits with ease. However, significant challenges remain for translating this technology into clinical applications. Traditional protein engineering methods, such as rational design, mutagenesis screens, and directed evolution, have been used to address issues like low efficacy, specificity, and high immunogenicity

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0013935117300452

[137] Environmental impacts of genetically modified plants: A review Debates about the commercial introduction of genetically modified (GM) crops started soon after the development of the first transgenic organism (1970s) which led to the development of guidelines for use of recombinant DNA by the US (United States) National Institute of Health (NIH, 2013). Generally, risks to the environment could be summarized as (1) risks associated with biodiversity including ecosystem functions effects on soil, and non-target species; (2) risks associated with gene flow and genetic recombination; and (3) risks associated with their evolution i.e. development of resistance either in insect pests or in weeds and Bacillus thuringiensis (Bt) crops. Firstly, toxicity produced by chemicals used with GM crops, is a big challenge to the environment as well as to the inherited plants (De Schrijver et al., 2015).

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https://www.sciencedirect.com/science/article/pii/S0045653522032441

[139] Genetically engineered microorganisms for environmental remediation Abstract In the recent era, the increasing persistence of hazardous contaminants is badly affecting the globe in many ways. Advances in newer remediation approaches may help enhance bioremediation's quality, while conventional procedures have failed to remove hazardous compounds from the environment. Thus, there has been a rise in the use of bioremediation due to an increase in environmental contamination, which led to the development of genetically engineered microbes (GEMs). GEMs are created by introducing a stronger protein into bacteria through biotechnology or genetic engineering to enhance the desired trait.

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scienceofbiogenetics

https://scienceofbiogenetics.com/articles/why-gene-editing-poses-ethical-concerns-and-raises-questions-about-morality

[140] Is Gene Editing Unethical? The Ethical Dilemmas Revealed - Genetics The ethical implications of gene editing have raised important questions about our moral responsibility in the realm of genetic manipulation and intervention. While gene editing can offer solutions to many genetic disorders and diseases, the ability to modify the human genome raises ethical questions about the limits of technological intervention. The ethical responsibility of using gene editing to alter the genetic makeup of organisms is significant, as it raises questions about playing the role of “nature” and potential unintended consequences. Gene editing, while holding the potential to cure genetic diseases and improve overall health, also raises concerns about the ethical implications and long-term consequences. Gene editing technology has become a powerful tool that allows scientists to modify an individual’s genetic material, raising questions about the ethical responsibility that comes with such capabilities.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC6751566/

[141] Moving Beyond 'Therapy' and 'Enhancement' in The Ethics of Gene Editing ... In one of the earliest papers on the subject, Leon Kass wrote that, regardless of clinical potential, gene editing raised profound ethical conundrums as “Genetic engineering…will be able to create new capacities, and hence establish new norms of health and fitness.”1 A huge literature has developed on the use of gene editing for purposes of biomedical enhancement, with passionate defenses of its potential and equally passionate criticisms of its potential harms.2 Even as research has progressed in different directions, much, if not most, work on gene editing in philosophical bioethics continues to focus on enhancement, including a number of articles in a recent special issue of this journal devoted to the topic.3 In a another recent paper on the topic, the authors affirmed that “Of greatest concern is editing of genes to confer advantageous traits not related to avoiding disease or preserving health.”4 Most statements on the use of gene editing in human beings so far from professional organizations, ethics boards, and advisory panels—including the recent exhaustive report by the United States National Academies of Science, Engineering, and Medicines—have called for drawing the line at “therapeutic” uses and forbidding “enhancement” with gene editing, thus reaffirming the centrality of the distinction.5

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https://www.sciencedirect.com/science/article/pii/S0160412016300824

[150] Next-generation ecological risk assessment: Predicting risk from ... Ecological risk assessment is the process of evaluating how likely it is that the environment may be impacted as the result of exposure to one or more chemicals and/or other stressors. This process should be playing a central role in environmental protection since basing regulatory decisions on evidence ought to be in the interests of all

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science

https://www.science.org/doi/10.1126/science.290.5499.2088

[151] The Ecological Risks and Benefits of Genetically Engineered Plants - AAAS Ecologists and other scientists have long expressed concerns about the potential impacts of releasing genetically engineered organisms (GEOs) into the environment (), while others emphasize their potential environmental benefits.The broad implications of national and international regulations underscore the policy and research communities' need for current scientific information and for

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https://www.sciencedirect.com/science/article/pii/S0045653522032441

[152] Genetically engineered microorganisms for environmental remediation Abstract In the recent era, the increasing persistence of hazardous contaminants is badly affecting the globe in many ways. Advances in newer remediation approaches may help enhance bioremediation's quality, while conventional procedures have failed to remove hazardous compounds from the environment. Thus, there has been a rise in the use of bioremediation due to an increase in environmental contamination, which led to the development of genetically engineered microbes (GEMs). GEMs are created by introducing a stronger protein into bacteria through biotechnology or genetic engineering to enhance the desired trait.

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toxigon

https://toxigon.com/regulatory-frameworks-for-genetic-engineering

[158] Regulatory Frameworks for Genetic Engineering - toxigon.com Regulatory Frameworks for Genetic Engineering Regulatory Frameworks for Genetic Engineering: Navigating the Complexities Regulatory Frameworks for Genetic Engineering: Navigating the Complexities Key Challenges in Regulating Genetic Engineering Today, we're diving deep into the world of regulatory frameworks for genetic engineering, exploring their importance, challenges, and future directions. In Africa, the regulatory frameworks for genetic engineering are still developing. Key Challenges in Regulating Genetic Engineering The potential for misuse of genetic engineering technologies is a real concern, and regulatory frameworks need to address these risks proactively. One of the most notable case studies in genetic engineering regulation is the use of CRISPR gene editing on crops. @article{regulatory-frameworks-for-genetic-engineering, title = {Regulatory Frameworks for Genetic Engineering}, url = {https://toxigon.com/regulatory-frameworks-for-genetic-engineering}

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC9583061/

[159] Genetically modified organisms: adapting regulatory frameworks for ... Most of the commercially available GM crops have been developed using transgenesis based on recombinant DNA technology, mainly to confer traits such as insect resistance, herbicide tolerance, and tolerance to abiotic stress (> 99% of total commercial traits) (Table 2) or other non-frequent traits related to improved food fortification such as provitamin A biosynthesis in “golden rice” and “golden banana”, or increased starch content in EH92-527–1 potato [9–13]. Following this line, the USA, despite being the main producer of GM crops in the world, does not have federal legislation as a general framework to regulate GMOs. Depending on whether the purpose of the GM product is for human, animal and/or environmental use, its authorization and regulation fall under the standards of the Food and Drug Administration (FDA); the Animal and Plant Health Inspection Service (APHIS); or the Department of Agriculture (USDA) and/or the USA Environmental Protection Agency (EPA), respectively.

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springer

https://link.springer.com/chapter/10.1007/978-981-97-5906-4_11

[161] Regulatory and Ethical Considerations | SpringerLink Key regulatory bodies such as the Food and Drug Administration (FDA) in the United States, the European Medicines Agency (EMA) in Europe, and the National Medical Products Administration (NMPA) in China play pivotal roles in evaluating the safety and efficacy of biomaterials intended for medical use. Ethical dilemmas may arise at various stages, including research involving human subjects, informed consent procedures, and equitable access to biomaterial-based therapies. By integrating regulatory compliance and ethical considerations into the development and utilization of biomaterials, we can harness their transformative potential while safeguarding human health and societal values. Download Article/Chapter or eBook Hunckler MD, Levine AD (2022) Navigating ethical challenges in the development and translation of biomaterials research. Download Article/Chapter or eBook

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cell

https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(24

[162] Risk-appropriate, science-based innovation regulations are important Inappropriate and often politicized regulations in many countries have limited the global benefits of agricultural biotechnology. The Cartagena Protocol on Biosafety (CPB) has proven to be one of the biggest barriers to biotechnological innovations, especially for food-insecure countries. The global movement of international agreements, such as the CPB, Convention on Biological Diversity, and

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fda

https://www.fda.gov/food/agricultural-biotechnology/how-gmos-are-regulated-united-states

[163] How GMOs Are Regulated in the United States | FDA - U.S. Food and Drug ... “GMO” (genetically modified organism) has become the common term consumers and popular media use to describe a plant, animal, or microorganism that has had its genetic material (DNA) altered through a process called genetic engineering. The U.S. Food and Drug Administration (FDA), U.S. Environmental Protection Agency (EPA), and U.S. Department of Agriculture (USDA) ensure that GMOs are safe for human, plant, and animal health. The Coordinated Framework for the Regulation of Biotechnology, established in 1986, describes how the agencies work together to regulate GMOs. In doing so, FDA makes sure that foods that are GMOs or have GMO ingredients meet the same strict safety standards as all other foods.

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cambridge

https://www.cambridge.org/core/journals/american-journal-of-law-and-medicine/article/synthetic-biology-state-regulation-in-the-biomedical-context/67E16C428EBCADD3CA2D89230C0A662F

[164] Synthetic Biology: State Regulation in the Biomedical Context Synthetic biology as used in the biomedical context is not regulated as a technology in the U.S.Footnote 9 Pursuant to the 1986 Coordinate Framework for Regulation of Biotechnology (“CFRB”), “synthetic biology, like earlier generations of biotechnology products…will be regulated based on particular product categories and particular uses.”Footnote 10 As a result, the U.S. Food and Drug Administration (“FDA”) is the federal regulatory agency with primary oversight of products developed using biotechnology, including synthetic biology, as they relate to drugs.Footnote 11 The FDA regulates drugs produced using synthetic biology with existing laws and guidance; most notably the Food, Drug, and Cosmetic Act of 1938 (“FDCA”) and its subsequent amendments.Footnote 12 Although the FDCA has been repeatedly applied to new technologies, synthetic biology and how it influences medical therapies presents an entirely new concern: organisms used in synthetic biology are often intended to multiply and can evolve while delivering treatment.Footnote 13 Further, some medical therapies developed using synthetic biology techniques are intended to reproduce within the body in order to deliver the desired treatment.Footnote 14 This raises questions as to how we should respond if a therapy developed using synthetic biology mutates into a pathogen.

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC7354896/

[167] The Importance and Future of Biochemical Engineering - PMC Broad challenges, for example, within this specific thematic area include: developing rules for hybrid biochemical/chemical conversion bioprocesses; predictive control of metabolic pathway spatial assembly; and the use of alternative biomanufacturing paradigms for enhancing biological conversion processes, such as microbial consortia, designed co-cultures, or cell-free systems. Other thematic areas include: bioprocess development for individualized medicine, forward-engineering for cellular control and predictable cell behaviors, which includes data-driven machine learning approaches for accelerating design, and engineering to understand & exploit new biology. | Topical Area (Green - Selected; Blue - Unselected) | Non-model organism development | Combining chemical catalysis with biochemical conversion | Bioprocess development for individualized medicine | Integration of mechanistic based models with data driven approaches for protein- and cell-based engineering | The biology and biotechnology of extracellular vesicles |

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC8147909/

[169] Recent Advances in Cellular and Molecular Bioengineering for Building ... In the field of cellular and molecular bioengineering (CMBE), engineering biological systems is one of the fastest-growing areas, especially with recent research breakthroughs simultaneously in multiple fields, including stem cell research, tissue engineering, gene editing, synthetic biology, omics, and biomanufacturing. Efforts have also been focused on engineering lymphoid cells and organs, including bone marrow, thymus tissue, and lymph nodes.49 For instance, recreating the bone marrow niche allows for the maintenance and expansion of the CD34+ cell population.28,65 Recapitulating the interaction of stromal cells (genetically engineered to express DLL1 for Notch activation) and human hematopoietic stem cells (HSCs) enables the long-term maintenance of lymphoid progenitors and improves the efficiency of differentiation and positive selection of human T cells.93 Activated B cells can be produced from engineered immune organoids mimicking the germinal center.2,67,74,80 The development of these in vitro systems provides an opportunity for investigating the physiology and pathology of immune systems and for

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nature

https://www.nature.com/articles/s44172-025-00345-1

[172] Machine learning empowered coherent Raman imaging and analysis for ... Apart from the traditional machine learning approach, deep learning algorithms based on U-Net were developed to improve SNR in SRS imaging49,51,52 With minor optimizations on the U-Net architecture developed previously by Ounkomol et al.53, CNN was applied to denoise the SRS data to improve the quality of biological images under low SNR conditions, such as low laser power (Fig. 1b)51. Furthermore, cell segmentation and classification based on the metabolic signatures of each cell obtained from hyperspectral SRS images was achieved by an SVM-based machine learning pipeline (Fig. 3c)73, validating the approach for high-throughput, semi-automatic analysis for basic research and clinical applications. J. Machine-learning-mediated single-cell classification by hyperspectral stimulated Raman scattering imaging: SPIE; 11900, 119000V (2021).

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sciencedirect

https://www.sciencedirect.com/science/article/pii/S0734975024001460

[175] Recent advances in engineering synthetic biomolecular condensates Over the past decade, numerous cellular compartments lacking a physical barrier, also referred to as biomolecular condensates or membraneless organelles (MLOs), composed of proteins and/or nucleic acids have been uncovered in the nucleus and cytoplasm, or on the membranes of eukaryotic cells (Lyon et al., 2021). To date, a great deal of attention has been paid to using natural or artificial proteins, and occasionally nucleic acids, for the construction of engineered macromolecular assemblies, i.e., synthetic biomolecular condensates or artificial MLOs, which generate exquisite biological tools for precisely manipulating cellular and metabolic processes in living cells. Corresponding theoretical and experimental results have uncovered the functions of protein condensates at different scales, such as regulating chemical reaction rates (molecular level), establishing medium-scale architectures (mesoscale level), and mediating subcellular localization (cellular level) (Lyon et al., 2021).

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nih

https://pmc.ncbi.nlm.nih.gov/articles/PMC3556414/

[178] The Bone Marrow Microenvironment as Niche Retreats for Hematopoietic ... The Bone Marrow Microenvironment as Niche Retreats for Hematopoietic and Leukemic Stem Cells - PMC This has been attributed to leukemia stem cells (LSCs), which occupy endosteal and sinusoidal niches in the bone marrow similar to those of hematopoietic stem cells (HSCs). These niches are complex, encompassing a broad range of bone marrow cells that includes bone lining cells (osteoblasts and osteoclasts), mesenchymal stem cells (MSCs), sinusoidal endothelium and perivascular stromal cells, immune cells, and several others that play different roles in HSC regulation . Uncertainty about which specific sinusoidal or endosteal niche cell is functionally important in producing any of these molecules and sufficient to maintain HSCs led Ding et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood.