Table of Contents
Overview
Definition and Significance
Genome editing refers to a collection of advanced techniques that enable precise modifications at the nucleotide level within the genomes of various organisms. This capability allows for the creation of directed mutations in virtually any genomic location, thereby facilitating significant advancements in genetic research and biotechnology.[1.1] Among the most notable genome editing technologies are meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system, which has emerged as a particularly powerful and accessible tool for genetic alterations.[3.1] The significance of genome editing lies not only in its technical capabilities but also in its potential applications across multiple fields, including medicine, agriculture, and environmental science. For instance, scientists are actively developing gene therapies that utilize genome editing to prevent and treat various diseases in humans, showcasing the technology's promise in clinical settings.[5.1] The CRISPR/Cas9 system, in particular, has revolutionized the field by providing a simpler, faster, and more cost-effective method for editing genomes compared to earlier techniques.[4.1] As genome editing technologies continue to evolve, their applications are expected to expand, potentially leading to greater public acceptance as the benefits of these technologies become more evident.[11.1] However, the public perception of genome editing is complex and can significantly influence its adoption and the development of ethical guidelines and regulatory frameworks.[12.1] Engaging in public dialogue about these technologies is crucial, as it fosters a better understanding of their implications and encourages inclusive discussions that consider diverse cultural and ethical perspectives.[14.1] Ultimately, the interplay between scientific advancement, ethical considerations, and public consultation is vital for the responsible development and application of genome editing technologies.[15.1]Applications in Various Fields
Genome editing technologies, particularly CRISPR-Cas9, have demonstrated significant potential across various fields, including medicine, agriculture, and biotechnology. In clinical medicine, genome editing is poised to revolutionize the treatment of genetic disorders. The ability to simultaneously correct or enhance multiple genetic loci suggests a broad range of applications, particularly in hematopoietic stem cells, which could lead to effective therapies for currently untreatable conditions.[16.1] Recent advancements in therapeutic gene editing have underscored the transformative potential of these technologies, with CRISPR-based methods emerging as powerful tools for precise modifications.[19.1] In the realm of gene therapy, the evolution of biological therapies has transitioned from traditional methods utilizing stem cells and viral vectors to innovative approaches involving RNA therapy and various genome editing tools.[18.1] The CRISPR-Cas9 system, in particular, has become the most effective and efficient method for genome editing, enabling precise modifications in living cells and facilitating the development of personalized medicine.[22.1] This technology's ability to create cell and animal models for hereditary diseases and cancer has further enhanced our understanding of disease mechanisms and potential treatment targets.[18.1] Agriculture is another field where genome editing is making significant strides. The application of these technologies allows for the development of crops with improved traits, such as disease resistance and enhanced nutritional profiles. The efficiency of CRISPR transfections leads to robust levels of editing, which can help avoid issues like mosaicism that may arise with older methods such as TALENs.[24.1] As public perception and acceptance of genome editing technologies evolve, particularly in food production, the potential for widespread application in agriculture continues to grow.[26.1]History
Evolution of Genome Editing Technologies
The evolution of genome editing technologies has been marked by significant milestones that have shaped the field. It began with advancements in eukaryotic DNA repair in the early 1990s, where pioneering studies demonstrated that inducing targeted double-strand breaks (DSBs) in mammalian cells could stimulate homologous recombination at specific sites. This foundational work established the concept of genome editing and paved the way for future innovations.[45.1] A major advancement came with the development of CRISPR-Cas9, a bacterial adaptive immune response system first identified in E. coli in 1987. Although the role of CRISPRs in bacterial immunity was not fully understood until the early 2000s, the CRISPR-Cas9 technology emerged in 2012, marking a pivotal moment in genome editing. It enabled targeted and precise manipulations of DNA sequences in living cells, becoming almost synonymous with gene editing.[55.1][56.1] Despite its prominence, CRISPR was not the first DNA editing technology.[56.1] The significance of CRISPR-Cas9 was further recognized when Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry in 2020 for their contributions to its development.[47.1] In response to the ethical implications of genome editing, particularly concerning human germline editing, the National Academy of Sciences and the National Academy of Medicine launched the Human Genome Editing Initiative in 2015. This initiative has facilitated discussions on the ethical frameworks surrounding such technologies and organized international summits to address advances and safety concerns.[46.1] Following controversial experiments, such as Jiankui's in 2019, calls for a moratorium on human embryo gene editing were reinforced, highlighting ongoing debates regarding the safety and ethical standards necessary for germline therapies.[46.1] As the technology has matured, it has expanded beyond basic research into practical applications, including agriculture. CRISPR technology has enabled precise genetic modifications in crops and livestock, enhancing traits such as disease resistance and climate adaptability.[53.1] The development of novel CRISPR-associated proteins and techniques, such as prime and base editing, has further improved the specificity and efficiency of genome editing, broadening its scope in agricultural practices.[54.1]Recent Advancements
CRISPR Technology
CRISPR technology has emerged as a revolutionary tool in the field of genome editing, significantly transforming various biological sciences. The origins of genome editing can be traced back to advancements in eukaryotic DNA repair, with pioneering studies in the early 1990s demonstrating that targeted double-strand breaks (DSBs) in mammalian cells could stimulate homologous recombination at specific genomic sites, thereby establishing the foundational concept of genome editing.[85.1] The most widely utilized genome editing technologies today include CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and homing endonucleases.[84.1] Among these, CRISPR-Cas9 has gained particular prominence due to its precision and efficiency, which have accelerated progress in crop breeding and other applications.[92.1] The technology allows for targeted modifications in the genome by employing a guide RNA (sgRNA) to direct the Cas9 protein to specific DNA sequences, facilitating precise edits.[83.1] Recent advancements in CRISPR technology have further enhanced its capabilities. Innovations such as prime editing and base editing have improved the specificity and efficiency of genome modifications, making CRISPR a cornerstone technology for addressing global challenges, including food security and climate change.[88.1] The transformative potential of CRISPR/Cas9 is particularly evident in agriculture, where it has been applied to develop disease-resistant crops and enhance traits such as drought tolerance and salinity resistance in various species, including wheat, rice, and soybean.[90.1] The recognition of CRISPR-Cas9's impact on genome editing was underscored by the awarding of the Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer A. Doudna for their pioneering work in developing this groundbreaking technology.[87.1] As research continues to evolve, CRISPR technology is expected to play an increasingly vital role in both basic and applied sciences, offering solutions to pressing agricultural and environmental challenges.Ethical Considerations
Societal Implications
Developments in genome editing technologies, particularly CRISPR/Cas9, have intensified ethical and regulatory discussions about their societal implications. These tools offer unprecedented precision in genetic modifications, raising complex ethical questions, especially regarding human germline editing, as changes in this area can be inherited by future generations.[122.1] The ethical discourse surrounding genome editing has gained renewed attention due to CRISPR's enhanced capabilities, making such editing more accessible and efficient compared to older technologies.[122.1] The ethical considerations focus on three main issues: the risks and uncertainties of the technology, responsibilities towards future generations, and the distinction between therapeutic and enhancement purposes of genome editing.[124.1] Concerns about social disparities and the ethical implications of authority over genetic changes are exacerbated by the potential for unintended consequences, such as "designer babies."[125.1] The current political landscape, differing from earlier bioethics debates, complicates the governance of genome editing technologies.[126.1] Public education and inclusive dialogue are crucial for shaping ethical frameworks that consider diverse cultural and religious perspectives, building societal consensus on gene editing advancements.[125.1] Human germline genome editing raises significant ethical concerns related to biodiversity and evolutionary processes, necessitating strict regulatory oversight due to complex bioethical issues.[125.1] While genome editing revives longstanding ethical questions about human life and eugenics, it also emerges in a political landscape different from the early 2000s, when bioethics was a major political controversy.[126.1] Despite rapid advancements, ethical issues in biotechnology have largely receded from public discourse, indicating a need for renewed engagement.[126.1] Understanding these complex ethical dilemmas requires examining the interplay between historical public perceptions and contemporary attitudes towards genetic engineering, particularly in light of past controversies surrounding cloning and embryonic stem cell research.[126.1]In this section:
Applications In Medicine
Targeted Therapies
Targeted therapies utilizing genome editing technologies have emerged as a transformative approach in the field of medicine, particularly in the treatment of genetic disorders, cancers, and infectious diseases. The development of genetic engineering in the 1970s laid the groundwork for these advancements, with significant progress made in the last decade through the application of engineered nucleases and CRISPR-Cas systems, which have demonstrated remarkable utility in various medical applications.[157.1] The advent of gene editing technologies, particularly CRISPR-based systems, has revolutionized the landscape of biomedical research and gene therapy. These technologies, including Zinc Finger Nucleases (ZFNs) and TAL Effector Nucleases (TALENs), have evolved significantly, leading to the development of CRISPR-Cas systems, which are now widely applied to create cellular and animal models for various hereditary and infectious diseases, as well as cancer.[157.1] The CRISPR-Cas9 system, discovered in 2012 by Doudna and Charpentier, has emerged as the most effective and accurate method for genome editing across all living cells, enabling precise modifications by simply providing the appropriate template.[174.1] Ongoing research has further advanced CRISPR technologies, introducing innovations such as base and prime editors that allow for precise nucleotide changes without generating harmful double-strand breaks (DSBs).[158.1] These advancements not only facilitate the identification of potential drug targets and therapeutic strategies but also pave the way for future "precise medication" approaches in treating various medical conditions.[157.1] The development of genetic engineering in the 1970s established a novel frontier in genome editing, enabling the manipulation of DNA and RNA.[156.1] Over the past decade, genome editing technologies, particularly those based on engineered nucleases, have rapidly evolved, demonstrating extraordinary utility across various fields, including basic research, biotechnology, and biomedical research.[156.1] CRISPR-Cas systems, derived from natural defense mechanisms in bacteria and archaea, have transformed genetic engineering by providing precision in DNA editing.[173.1] These systems facilitate targeted DNA alterations through the generation of double-stranded breaks (DSBs), which stimulate efficient cellular DNA recombination mechanisms in mammalian cells.[156.1] The repair of these DSBs can occur via two primary pathways: homology-directed repair (HDR) and nonhomologous end-joining (NHEJ), resulting in either targeted integration or gene disruption.[156.1] Furthermore, ongoing research has led to the rapid iteration of CRISPR technologies, such as base and prime editors, which enable precise nucleotide changes without the need for generating harmful DSBs, thereby enhancing the efficiency, safety, and versatility of genome editing.[159.1] Despite the promise of genome editing in targeted therapies, challenges remain, particularly regarding the delivery of these tools to target tissues effectively and safely. The large size and negative charge of CRISPR components, along with their immunogenic potential, pose significant hurdles for in vivo applications.[161.1] Moreover, the transient expression of genome editing tools is crucial to minimize off-target effects and genotoxicity, necessitating the development of optimized delivery strategies.[162.1] To ensure equitable access to genome editing therapies, particularly for marginalized communities, it is essential to establish robust regulatory frameworks and health systems that can support the development, approval, and delivery of these advanced therapies. Addressing potential disparities in access requires a human rights-based approach that emphasizes health equity throughout all phases of genome therapy implementation.[180.1]Clinical Trials and Research
Clinical trials involving genome editing technologies, particularly CRISPR-Cas9, have shown promising results in treating various hereditary diseases. One notable study focused on Interstitial Lung Disease, where CRISPR/Cas9 components were delivered directly into the amniotic fluid, resulting in the in utero inactivation of the pathogenic SftpcI73T mutant allele. This intervention significantly improved survival rates and reduced lung fibrosis in SftpcI73T transgenic mice, highlighting the potential of in utero gene editing as a therapeutic strategy.[177.1] Moreover, advancements in CRISPR-based genome editing have led to significant improvements in the clinical care of patients with inherited hematologic disorders. Research conducted by Almotiri, Rodrigues, and colleagues emphasizes the experimental progress in editing hematopoietic stem cells, which has the potential to transform treatment paradigms for these conditions.[179.1] Despite these advancements, the long-term risks associated with gene therapy remain inadequately understood. A comprehensive evaluation of safety outcomes from 38 T cell therapy trials, involving 783 patients over more than 2,200 total patient-years of observation, revealed that the risks of gene therapy, particularly those utilizing integrating gammaretroviral or lentiviral vectors, are still being assessed.[167.1] Ethical considerations also play a crucial role in the discourse surrounding germline genome editing (GGE). The American National Academies of Sciences, Engineering, and Medicine have indicated that clinical research using GGE should be permitted, provided that a regulatory framework is established to manage societal risks, such as the potential misuse of GGE for non-medical enhancements.[164.1] Furthermore, ethical discussions have consistently highlighted three primary concerns: the risks and uncertainties of the technology, the implications of interfering with the human germline, and the legitimacy of genome editing in the context of therapy versus enhancement.[165.1]In this section:
Applications In Agriculture
Crop Improvement
Genome editing technologies, particularly CRISPR/Cas systems, have revolutionized crop improvement by enabling precise genetic modifications that enhance various traits in plants. These advancements allow for the development of crops that are more resilient to environmental stressors, possess higher nutritional content, and require fewer resources for cultivation.[198.1] The ability to make targeted changes at specific loci in the genome facilitates the modulation of traits such as yield, quality, disease resistance, and herbicide tolerance.[195.1] The advent of genome editing technologies, particularly the CRISPR/Cas system, has revolutionized plant molecular biology, enabling precise genetic manipulation of crops with high target specificity and programmability.[193.1] This progress has facilitated the development of germplasms with beneficial traits, which is essential for creating more sustainable agricultural systems.[193.1] Notably, genome editing allows plant breeders to introduce new traits into crops, addressing the needs of a growing global population and adapting to changing environmental conditions.[194.1] Advanced techniques such as base editing and prime editing have further enhanced the precision of genetic alterations, allowing for targeted modifications that were previously challenging to achieve.[197.1] For example, genome editing has been successfully employed to develop soybeans that produce healthier oils, demonstrating its potential to meet both health and agricultural demands.[194.1] Overall, the advancements in genome editing are pivotal in increasing plant yield, quality, disease resistance, and herbicide resistance, thereby contributing significantly to sustainable agricultural practices.[193.1] The challenges of global food security are becoming increasingly pronounced due to rising populations, the impacts of climate change on crop production, and the limited availability of land for agricultural expansion. These factors impose significant stresses on plants, making them more susceptible to diseases and productivity losses caused by pathogens, pests, and weeds.[201.1] Traditional breeding strategies are proving inadequate for the rapid development of new plant traits necessary to counteract these productivity declines. In this context, modern advances in genome editing offer timely and effective methods to optimize crop plants, thereby enhancing their resilience and sustainability.[200.1] The potential of genome editing extends beyond mere trait enhancement; it plays a crucial role in addressing broader challenges related to food security and nutrition, highlighting the urgency for societal acceptance and support of these technologies.[196.1] However, the implementation of genome editing in agriculture also raises ethical considerations, particularly regarding the implications of genetic modifications on biodiversity and animal welfare.[202.1] As such, while the potential benefits of genome editing in crop improvement are substantial, they must be balanced with careful consideration of the associated social and ethical issues.[191.1]In this section:
Challenges And Limitations
Technical Challenges
The application of CRISPR-Cas9 technology in genome editing faces significant technical challenges, particularly concerning off-target effects, which are unintended genetic alterations at sites other than the intended target.[247.1] These off-target effects can result in the introduction of new genetic mutations rather than correcting existing ones, potentially disrupting normal cellular functions and leading to adverse conditions or diseases.[248.1] The specificity of the single guide RNA (sgRNA) plays a crucial role in determining off-target sites, as Cas9 is known to tolerate up to three mismatches between the sgRNA and the genomic DNA.[249.1] Furthermore, while researchers have made strides in enhancing the precision of CRISPR by developing more accurate Cas9 variants and optimizing guide RNA designs, the reliance on double-strand breaks (DSBs) can introduce significant safety issues, including cell death and chromosomal disorganization, which may increase the risk of malignant tumors.[264.1] Consequently, there is a growing focus on developing CRISPR systems that do not rely on DSBs, such as base editing and prime editing, which hold promise for safer gene editing applications.[264.1] The application of CRISPR-based gene editing in clinical settings faces significant technical challenges, particularly in mitigating off-target effects, which are unintended genetic alterations at sites other than the intended target.[264.1] Researchers have made substantial progress in enhancing the precision of CRISPR by developing more precise Cas9 variants and optimizing guide RNA designs.[264.1] However, the reliance on double-strand breaks (DSBs) during the editing process can lead to serious safety issues, including cell death, large base deletions, and chromosomal disorganization, which may increase the risk of malignant tumors.[264.1] To address these concerns, there is a growing focus on CRISPR systems that do not introduce DSBs, such as base editing and prime editing, which facilitate gene editing without the associated risks of DSBs and hold significant potential for future gene therapy applications.[264.1] Recent advancements have also introduced alternative genome-editing techniques, such as prime editing and base editing, which do not require DSBs and can facilitate gene editing with greater precision. These methods allow for a range of genetic modifications, from single nucleotide changes to larger insertions, thereby expanding the potential applications of gene therapy while minimizing the associated risks of traditional CRISPR-Cas9 systems.[264.1]Ethical and Social Concerns
The ethical and social concerns surrounding genome editing are multifaceted and significant. One of the primary issues is the potential for inequity in access to these advanced therapies. High costs and a lack of access to somatic gene therapies raise critical questions about health equity, sovereignty, and racial justice, particularly in the context of heritable genome editing, which has the potential to alter genetic traits across generations.[239.1] Furthermore, various impediments, such as inadequate regulatory capacity, manufacturing shortages, and health literacy deficits, could restrict global patient access to genome therapies. A human rights-based approach is essential to ensure equitable access, emphasizing the need for robust health systems and regulatory frameworks that govern these therapies at the national level.[240.1] The discourse on genome editing also highlights the necessity of addressing ethical implications alongside scientific advancements. Adopting a purely scientific perspective risks overlooking the societal and equity considerations that are crucial for responsible governance in this field.[241.1] To mitigate these concerns, it is vital to increase the representation of underrepresented groups in research and clinical studies. This includes prioritizing the recruitment of diverse participants, engaging communities to build trust, and ensuring that genomic services are accessible to underserved populations.[242.1] In the agricultural sector, the application of genome editing technology offers significant benefits, including increased crop yields and enhanced disease resistance. However, it also introduces a range of ethical and social issues, particularly concerning intellectual property rights and the equitable distribution of benefits among various stakeholders, such as farmers, consumers, and multinational corporations.[228.1] The ongoing discourse surrounding genome editing emphasizes the importance of addressing these social and ethical dilemmas to ensure that the technology contributes positively to food security and environmental health.[228.1] Furthermore, it is crucial to consider regulatory, ethical, social, and biosafety concerns to facilitate the safe and responsible development and use of genome-edited crops.[246.1]References
[1] Genome Editing - an overview | ScienceDirect Topics — Genome editing represents a group of newly developed capabilities that allow nucleotide-level targeting of genomic regions in a wide range of species. This chapter provides an overview of these technologies which open the possibility of creating directed mutations in virtually any location of the genome.
[3] Summary - Human Genome Editing - NCBI Bookshelf — Genome editing2 is a powerful new tool for making precise additions, deletions, and alterations to the genome—an organism's complete set of genetic material. The development of new approaches—involving the use of meganucleases; zinc finger nucleases (ZFNs); transcription activator-like effector nucleases (TALENs); and, most recently, the CRISPR/Cas9 system—has made editing of the genome
[4] A The Basic Science of Genome Editing - National Center for ... — The first such system to be developed for use in genome editing of human cells, known as CRISPR/Cas9, is based on RNA-guided targeting and is much simpler, faster, and cheaper than earlier methods. Following the initial generation of mice carrying targeted mutations of the β2-microglubulin and the c-Abl gene (Schwartzberg et al., 1989; Zijlstra et al., 1989), homologous recombination in ES cells has become a widely used tool for the study of mammalian development and the generation of animal models of human genetic diseases (Solter, 2006). haESCs contain only one copy of allelic genes of diploid cells and are amenable to genetic modification with traditional gene-targeting approaches and with new nuclease-based genome-editing strategies (Li et al., 2012, 2014).
[5] What is genome editing? - National Human Genome Research Institute — Scientists are developing gene therapies - treatments involving genome editing - to prevent and treat diseases in humans. These scientists did not use CRISPR to treat Layla, and instead used another genome editing technology called TALENs. Doctors tried many treatments before this, but none of them seemed to work, so scientists received special permission to treat Layla using gene therapy. Scientists are developing gene therapies - treatments involving genome editing - to prevent and treat diseases in humans. These scientists did not use CRISPR to treat Layla, and instead used another genome editing technology called TALENs. Doctors tried many treatments before this, but none of them seemed to work, so scientists received special permission to treat Layla using gene therapy.
[11] Public Perception of Genome Editing: A Global Perspective in 2025 — Advances in Technology: Continued advancements in genome editing technologies are likely to expand their applications and potential benefits. This could lead to greater public acceptance as the technology becomes more familiar and its benefits more apparent. ... The public perception of genome editing is a complex and dynamic landscape. As we
[12] Citizen views on genome editing: effects of species and purpose - Springer — Public opinion can affect the adoption of genome editing technologies. In food production, genome editing can be applied to a wide range of applications, in different species and with different purposes. This study analyzed how the public responds to five different applications of genome editing, varying the species involved and the proposed purpose of the modification. Three of the
[14] A decade of public engagement regarding human germline gene editing: a ... — The WHO indicates that the public dialogue on HGGE has to be conducted nationally, given the various historical, cultural and religious contexts, but also stresses the need for a global approach when it comes to governance measures This raises important questions, such as how to involve everyone with a stake in the human genome Continued attention to these profound questions is needed to ensure ethical values and principles such as social justice, solidarity and global health justice that underpin decisions made This includes for example “A commitment to equitable access to opportunities and potentially beneficial outcomes from human genome editing for all people, particularly those living in low- and middle-income countries” On a study level, multiple sampling strategies were described to increase inclusivity, diversity and representativeness.
[15] Genome editing: science, ethics, and public engagement — Perhaps the overarching message from the fast-evolving work of human genome editing lies in the importance of engagement: the interdependence of science, ethics, and public consultation.
[16] Genome editing in clinical practice: A model study for next-gen ... — It may allow the simultaneous correction or enhancement of multiple genetic loci. Thus, we envision a broad range of applications for clinical medicine. Today, the future of genomic medicine appears bright. The seminal study by Lydeard et al. should help the field on the way toward clinical GE in hematopoietic stem cells.
[18] Genome Editing in Medicine: Tools and Challenges - PMC — Over the years biological therapy evolved from using stem cells and viral vectors to RNA therapy and testing different genome editing tools as promising gene therapy agents. These genome editing technologies (Zinc finger nucleases, TAL effector nucleases), specifically CRISPR-Cas system, revolutionized the field of genetic engineering and is widely applied to create cell and animal models for various hereditary, infectious human diseases and cancer, to analyze and understand the molecular and cellular base of pathogenesis, to find potential drug/treatment targets, to eliminate pathogenic DNA changes in various medical conditions and to create future “precise medication”. | Refractory herpetic viral keratitis | Herpes simplex virus type I genome | Gene editing (CRISPR-Cas9) | BD111 | Active clinical trial, not recruiting potential participants yet | https://clinicaltrials.gov/ct2/show/NCT04560790?term=gene+editing &draw=2&rank=1 https://crisprmedicinenews.com/clinical-trial/herpes-simplex-virus-refractory-keratitis-nct04560790/ |
[19] Recent Therapeutic Gene Editing Applications to Genetic Disorders — Recent years have witnessed unprecedented progress in therapeutic gene editing, revolutionizing the approach to treating genetic disorders. In this comprehensive review, we discuss the progression of milestones leading to the emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)-based technology as a powerful tool for precise and targeted modifications of the
[22] Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing — It was in 2012 that Doudna, J, and Charpentier, E discovered CRISPR/Cas-9 could be used to edit any desired DNA by just providing the right template.8 Since then, CRISPR/Cas-9 becomes the most effective, efficient, and accurate method of genome editing tool in all living cells and utilized in many applied disciplines.9 Thus, this review aims to discuss the mechanisms of genome editing mediated by CRISPR/Cas-9 and to highlight its recent applications as one of the most important scientific discoveries of this century, as well as the current barriers to the transformation of this technology. doi: 10.1016/j.cell.2014.05.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
[24] How Does CRISPR Compare with Other Gene-Editing Methods? — But sometimes forgotten in the midst of the CRISPR furor are the gene-editing methods that came before, such as naturally occurring meganucleases, and the sequence-specific engineered zinc finger nucleases (ZFN) or TALENS. All components are delivered to the cell using standard molecular biology techniques so gene editing can be performed within the technical capabilities of most laboratories—and as CRISPR transfections have a higher efficiency, this results in robust levels of editing, and avoids mosaicism that can sometimes occur with TALENs. There is a greater tolerance for mismatch of the sgRNA to the target site compared to TALENs, which can result in off-target activity.4 But this can be reduced with careful selection of the sgRNA—there are several computational models that have been developed to help select the most specific and efficient sgRNA for your experiment.
[26] Citizen views on genome editing: effects of species and purpose - Springer — Public opinion can affect the adoption of genome editing technologies. In food production, genome editing can be applied to a wide range of applications, in different species and with different purposes. ... Bearth, A., and M. Siegrist. 2016. Are risk and benefit perceptions more important for public acceptance of innovative food technologies
[45] Past, present, and future of CRISPR genome editing technologies — Genome editing originally arose from advancements in the field of eukaryotic DNA repair. Pioneering studies in the early 1990s using homing endonucleases such as I-SceI, which recognizes 18-bp DNA sequences, showed that induction of a targeted double-strand break (DSB) in mammalian cells stimulated homologous recombination at the target site. 2 This established the concept of genome editing
[46] Gene Editing: Developments, Ethical Considerations, and Future ... — With the advent and patenting of CRISPR technology, the National Academy of Science and the National Academy of Medicine launched the Human Genome Editing Initiative in 2015 to create an informed decision-making process on germline editing experiments.4 The initiative has organized three international summits that convene experts in the field to discuss advances and ethical frameworks for such technologies. Because of Jiankui’s 2019 experiment, The National Institutes of Health, expert bioethicists, and many pioneers of CRISPR technology called for a temporary moratorium on all human-based embryo gene editing.11 The organizing committee of the Third International Summit on Human Genome Editing reaffirmed this decision in 2023, stating that human germline editing is not acceptable since safety, ethical, and government standards have not been met for implementation of germline therapies.12
[47] The evolution and history of gene editing technologies — Furthermore, the technology was used for a genome wide study to identify genes involved in resistance to SARS-Cov2. 135 Additionally, the 2020 Nobel prize in Chemistry has recently been awarded to Emmanuelle Charpentier and Jennifer Doudna for "the development of a method for genome editing."
[53] CRISPR in Agriculture: 2024 in Review - Innovative Genomics Institute (IGI) — Just 12 years after its development, the genome-editing tool CRISPR is being used in a wide breadth of ways in plant and animal agriculture – from reducing waste to adapting plants and animals to climate change, from making plants that naturally resist weeds to ones that can be harvested more efficiently, from food to biofuels and paper. A research group based at the University of Maryland developed a modified CRISPR-Cas system that they called CRISPR-Combo that lets scientists edit genes and turn them “on” – meaning, get the cell making the protein encoded by the gene – at the same time.
[54] Recent advances of CRISPR-based genome editing for enhancing staple ... — This review highlights the transformative potential of CRISPR/Cas technology, emphasizing recent innovations such as prime and base editing, and the development of novel CRISPR-associated proteins, which have significantly improved the specificity, efficiency, and scope of genome editing in agriculture. These advancements enable targeted
[55] A Brief History of CRISPR-Cas9 Genome-Editing Tools - Bitesize Bio — A Brief History of CRISPR-Cas9 Genome-Editing Tools. CRISPR-Cas9 is a bacterial adaptive immune response system that has been harnessed as a precise genome editing tool. CRISPRs were first identified in E. coli in 1987, but the role of CRISPRs bacterial immunity was not identified until the early 2000s. ... In 2020, this technology earned
[56] CRISPR: History and perspectives to the future - ScienceDirect — CRISPR/Cas9 technology emerged in 2012. Since then, the techniques for targeted and precise manipulations of DNA sequences in living cells have played a crucial and dominant role in biology. Although CRISPR has become almost a synonym with gene editing, it is not a new concept and not nearly the first technology developed to edit DNA.
[83] PDF — Historical background Genome editing originally arose from advancements in the field of eukaryotic DNA repair. Pioneering studies in the early 1990s ... the development of CRISPR genome editing technologies, whereby targeting Cas9 to a specific genomic site could thus be achieved by designing an sgRNA with a matching
[84] Genome-Editing Technologies: Principles and Applications — The core technologies now most commonly used to facilitate genome editing, shown in Figure 1, are (1) clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), (2) transcription activator-like effector nucleases (TALENs), (3) zinc-finger nucleases (ZFNs), and (4) homing endonucleases or meganucleases. Alternatively, in the presence of a donor template with homology to the targeted chromosomal site, gene integration, or base correction via homology-directed repair (HDR) can occur (HDR) (Fig. 2B) (see Fig. 2 for an overview of other possible genome-editing outcomes) (Bibikova et al. Dimerization of the ZFN proteins is mediated by the FokI cleavage domain, which cuts DNA within a five- to seven-bp spacer sequence that separates two flanking zinc-finger binding sites (Smith et al.
[85] Past, present, and future of CRISPR genome editing technologies — Genome editing originally arose from advancements in the field of eukaryotic DNA repair. Pioneering studies in the early 1990s using homing endonucleases such as I-SceI, which recognizes 18-bp DNA sequences, showed that induction of a targeted double-strand break (DSB) in mammalian cells stimulated homologous recombination at the target site. 2 This established the concept of genome editing
[87] Recent Advances in Genome-Engineering Strategies - PubMed — Recent Advances in Genome-Engineering Strategies Genes (Basel). 2023 Jan 2;14(1):129. doi: 10.3390/genes14010129. ... chemistry Nobel Prize was awarded to Emmanuelle Charpentier and Jennifer A. Doudna for the discovery of a new promising genome-editing tool: the genetic scissors of CRISPR-Cas9.
[88] Frontiers | Recent advances of CRISPR-based genome editing for ... — This review highlights the transformative potential of CRISPR/Cas technology, emphasizing recent innovations such as prime and base editing, and the development of novel CRISPR-associated proteins, which have significantly improved the specificity, efficiency, and scope of genome editing in agriculture. This detailed understanding of the CRISPR/Cas mechanism underscores its effectiveness in enabling precise and efficient genome modifications, making it a cornerstone technology for advancing crop traits and addressing global challenges such as food insecurity and climate change (Raza et al., 2024). Citation: Chen F, Chen L, Yan Z, Xu J, Feng L, He N, Guo M, Zhao J, Chen Z, Chen H, Yao G and Liu C (2024) Recent advances of CRISPR-based genome editing for enhancing staple crops.
[90] CRISPR/Cas9-based genome editing: A revolutionary approach for crop ... — CRISPR/Cas9-based genome editing: A revolutionary approach for crop improvement and global food security - ScienceDirect In this review we will discuss a general overview CRISPR/Cas9, its mechanism and recent application of CRISPR/Cas9 in plants with special focus on disease resistance and stress tolerance enhancement, challenges and future perspective of CRISPR/Cas9 gene editing technology in agriculture field. This review will provide a holistic perspective on the role of CRISPR/Cas9-mediated genome editing in crop improvement and its implications for global food security, serving as a valuable resource for researchers, policymakers, and stakeholders in the agricultural sector. The CRISPR/Cas9 genome editing technology has become a promising tool to enhance various traits in plants, enabling them to become more tolerant and better suited to withstand the challenges posed by biotic and abiotic stress .
[92] CRISPR-Cas9 in Agriculture: Improving Crops and Livestock — CRISPR-Cas9 technology has been widely applied in agriculture to improve crop quality, increase food productivity, and enhance livestock characteristics. The technology has accelerated crop breeding progress due to its precision in specific gene editing, with a significant increase in the number of publications using CRISPR-Cas9 for crop improvement in recent years. The application of CRISPR
[122] 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.
[124] Human germline editing in the era of CRISPR-Cas: risk and uncertainty ... — Three problems regarding germline therapies have been consistently discussed in ethics and law: (i) questions of risk and uncertainty related to the technology and its application, (ii) interference with the human germline and responsibility towards future generations, and (iii) the legitimization of genome editing measures with regard to the concepts of therapy and enhancement. In the following, we examine potential implications of the CRISPR-Cas technology for an evaluation of the three major ethical and legal problem complexes regarding human germline editing, i.e. questions of risk and uncertainty, inter-generational responsibility, and therapeutic legitimacy. Scenario 2 overcomes the normative problem of passing on genetic modifications in the germline of individual human beings to future generations and exposing future human beings, i.e. descendants of edited embryos, to unknown, possibly negative long-term effects without their consent, as well as affecting the human gene pool and, thus, humanity as a whole.
[125] Ethical Concerns: Germline Gene Editing in Babies — Public education and inclusive dialogue are vital for shaping ethical frameworks, addressing diverse cultural and religious perspectives, and building societal consensus on gene editing advancements. Gene editing, particularly human germline genome editing, has emerging implications for biodiversity and evolutionary processes, necessitating environmental effects in ethical discussions. Gene editing, particularly human germline genome editing as applied to embryos, is a space that requires strict regulatory oversight due to the significant bioethical issues and ethical concerns at play. Gene editing, especially in human embryos, raises deep ethical concerns that need strong frameworks to guide decision-making. Primary worries regarding human genome editing include the potential for ‘designer babies,’ increasing social disparities, and unintended genetic effects, raising ethical concerns about who should be allowed to make germline gene editing changes.
[126] Genome Editing, Ethics, and Politics - PMC — Rather, while genome editing raises old ethical questions about the value of human life, eugenics, and the weight of unintended consequences, CRISPR also came into being in a political landscape that vastly differs from the early aughts when bioethics was last a major topic of political controversy. For the better part of a dozen years and over 3 US presidential terms, heated debates about the ethics of cloning and embryonic stem cell research helped to define the American political landscape.1 Yet now, despite the fact that new developments like gene editing are barreling ahead and challenges to traditional conceptions of human reproduction are still in development, ethical issues of biotechnology have largely disappeared from the public space.
[156] Applications of genome editing technology in the targeted therapy of ... — In the 1970s, the development of genetic engineering (manipulation of DNA or RNA) established a novel frontier in genome editing.1 Based on engineered or bacterial nucleases, genome editing technologies have been developed at a rapid pace over the past 10 years and have begun to show extraordinary utility in various fields, ranging from basic research to applied biotechnology and biomedical research.2 Genome editing can be achieved in vitro or in vivo by delivering the editing machinery in situ, which powerfully adds, ablates and “corrects” genes as well as performs other highly targeted genomic modifications.3,4 Targeted DNA alterations begin from the generation of nuclease-induced double-stranded breaks (DSBs), which leads to the stimulation of highly efficient recombination mechanisms of cellular DNA in mammalian cells.5,6 Nuclease-induced DNA DSBs can be repaired by one of the two major mechanisms that occur in almost all cell types and organisms: homology-directed repair (HDR) and nonhomologous end-joining (NHEJ),7 resulting in targeted integration or gene disruptions, respectively (Fig. 1).
[157] Genome Editing in Medicine: Tools and Challenges - PMC — Over the years biological therapy evolved from using stem cells and viral vectors to RNA therapy and testing different genome editing tools as promising gene therapy agents. These genome editing technologies (Zinc finger nucleases, TAL effector nucleases), specifically CRISPR-Cas system, revolutionized the field of genetic engineering and is widely applied to create cell and animal models for various hereditary, infectious human diseases and cancer, to analyze and understand the molecular and cellular base of pathogenesis, to find potential drug/treatment targets, to eliminate pathogenic DNA changes in various medical conditions and to create future “precise medication”. | Refractory herpetic viral keratitis | Herpes simplex virus type I genome | Gene editing (CRISPR-Cas9) | BD111 | Active clinical trial, not recruiting potential participants yet | https://clinicaltrials.gov/ct2/show/NCT04560790?term=gene+editing &draw=2&rank=1 https://crisprmedicinenews.com/clinical-trial/herpes-simplex-virus-refractory-keratitis-nct04560790/ |
[158] Recent advances in therapeutic gene editing technologies — The advent of gene editing technologies, particularly CRISPR-based systems, has revolutionized the landscape of biomedical research and gene therapy. Ongoing research in gene editing has led to the rapid iteration of CRISPR technologies, such as base and prime editors, enabling precise nucleotide changes without the need for generating harmful double-strand breaks (DSBs). Furthermore
[159] Therapeutic precision, potency and promise | Nature Biomedical Engineering — Nature Biomedical Engineering - Advances in base editing and prime editing, coupled with optimized delivery strategies, are enhancing the efficiency, safety and versatility of genome editing for
[161] Non-viral systems for intracellular delivery of genome editing tools — Specific and efficient delivery of genome editing tools to target cells is one of the key elements of such technologies. ... The major challenges of such delivery inherent for genome editing tools include a large size of CRISPR/Cas or TALEN components, a large negative charge of RNAs, immunogenic potential, low efficacy, and off-target side
[162] The delivery challenge: fulfilling the promise of therapeutic genome ... — Another major challenge is that genome editing tools should ideally be transiently expressed in target cells because a long duration of activity raises concerns of off-target nuclease genotoxicity
[164] Risks and benefits of human germline genome editing: An ethical ... — Risks and benefits of human germline genome editing: An ethical analysis - PMC We also show that the societal risks of the procedure, i.e. genetic enhancement, are manageable by establishing a regulative framework before the GGE is implemented. In their report Human Genome Editing: Science, Ethics, and Governance, the American National Academies of Science, Engineering, and Medicine have stated that clinical research using germline genome editing (GGE) in humans should be permitted (The National Academies 2017). The main societal risk is seen in the possible misuse of GGE for non-medically indicated purposes such as genetic enhancement. If one considers the zygote as eukaryotic, diploid cell, it is unproblematic to call GGE disease prevention, since, analogous to sperm cell and oocyte-editing, a future individual is prevented from inheriting a monogenic disease.
[165] Human germline editing in the era of CRISPR-Cas: risk and uncertainty ... — Three problems regarding germline therapies have been consistently discussed in ethics and law: (i) questions of risk and uncertainty related to the technology and its application, (ii) interference with the human germline and responsibility towards future generations, and (iii) the legitimization of genome editing measures with regard to the concepts of therapy and enhancement. In the following, we examine potential implications of the CRISPR-Cas technology for an evaluation of the three major ethical and legal problem complexes regarding human germline editing, i.e. questions of risk and uncertainty, inter-generational responsibility, and therapeutic legitimacy. Scenario 2 overcomes the normative problem of passing on genetic modifications in the germline of individual human beings to future generations and exposing future human beings, i.e. descendants of edited embryos, to unknown, possibly negative long-term effects without their consent, as well as affecting the human gene pool and, thus, humanity as a whole.
[167] Long-term safety of lentiviral or gammaretroviral gene ... - Nature — Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy
[173] CRISPR-Cas Systems: Mechanisms and Gene Editing Applications — The CRISPR-Cas systems have transformed genetic engineering, offering precision in DNA editing. Derived from a natural defense mechanism in bacteria and archaea, these systems allow for accurate gene manipulation.
[174] Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing — It was in 2012 that Doudna, J, and Charpentier, E discovered CRISPR/Cas-9 could be used to edit any desired DNA by just providing the right template.8 Since then, CRISPR/Cas-9 becomes the most effective, efficient, and accurate method of genome editing tool in all living cells and utilized in many applied disciplines.9 Thus, this review aims to discuss the mechanisms of genome editing mediated by CRISPR/Cas-9 and to highlight its recent applications as one of the most important scientific discoveries of this century, as well as the current barriers to the transformation of this technology. doi: 10.1016/j.cell.2014.05.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
[177] Genome Editing for Rare Diseases - PMC - PubMed Central (PMC) — In a landmark study for Interstitial Lung Disease, the delivery of CRISPR/Cas9 genome-editing components directly into the amniotic fluid led to in utero inactivation of the pathogenic SftpcI73T mutant allele, improving survival and decreasing lung fibrosis in SftpcI73T transgenic mice . This study raises the possibility that in utero gene
[179] Treating genetic blood disorders in the era of CRISPR-mediated genome ... — The review from Almotiri, Rodrigues, and colleagues highlights the experimental advances in CRISPR-based genome editing of hematopoietic stem cells that led to significant improvements in the clinical care of patients with inherited hematologic disorders. The challenges of using CRISPR-mediated genome editing in patients are also outlined and solutions forwarded.
[180] Navigating equity in global access to genome therapy expanding access ... — Potential impediments such as countries’ lack of regulatory capacity to evaluate these advanced therapies, a shortage of manufacturing capabilities for genome therapy production, inadequate data infrastructures for the protection of sensitive genome information, health literacy deficits impeding comprehension of treatment benefits and risks, and deficient public health systems and workforce, could globally restrict patient access. A human rights-based approach to global access to sickle cell disease genome therapy underscores the importance of robust health systems and a regulatory framework to govern cell and gene therapies at the national level. To ensure global equitable access to SCD genome therapies, it is necessary to guide all phases - from research and development to regulatory approval, manufacturing, and delivery - by principles of human rights and health equity.
[191] Genome editing and sustainable agriculture - Nature Sustainability — Genome editing and sustainable agriculture | Nature Sustainability nature The application of genome editing technology in agriculture is clearly beneficial; however, it also opens doors for a host of associated social and ethical issues, such as intellectual property rights associated with the use of the technology and the question of who benefits from such crops in terms of the stakeholders involved, such as farmers, consumers and multinational corporations. The ongoing debate on the promise of genome editing technology and its associations with other approaches in agriculture towards improving food security and ecosystem and environmental health is interesting and relevant to sustainability.
[193] Applications of CRISPR-Cas in agriculture and plant biotechnology — 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 molecular cell biology review articles article Review Article Published: 24 September 2020 Applications of CRISPR–Cas in agriculture and plant biotechnology Haocheng Zhu1,2 na1, Chao Li1,2 na1 & Caixia Gao ORCID: orcid.org/0000-0003-3169-82481,2 Nature Reviews Molecular Cell Biology volume 21, pages 661–677 (2020)Cite this article 62k Accesses 144 Altmetric Metrics details Subjects Molecular engineering Plant molecular biology An Author Correction to this article was published on 04 November 2020 A Publisher Correction to this article was published on 12 October 2020 This article has been updated Abstract The prokaryote-derived CRISPR–Cas genome editing technology has altered plant molecular biology beyond all expectations. Characterized by robustness and high target specificity and programmability, CRISPR–Cas allows precise genetic manipulation of crop species, which provides the opportunity to create germplasms with beneficial traits and to develop novel, more sustainable agricultural systems. Furthermore, the numerous emerging biotechnologies based on CRISPR–Cas platforms have expanded the toolbox of fundamental research and plant synthetic biology. In this Review, we first briefly describe gene editing by CRISPR–Cas, focusing on the newest, precise gene editing technologies such as base editing and prime editing. We then discuss the most important applications of CRISPR–Cas in increasing plant yield, quality, disease resistance and herbicide resistance, breeding and accelerated domestication.
[194] Genome Editing in Agricultural Biotechnology | FDA — Genome Editing in Agricultural Biotechnology | FDA Genome Editing in Agricultural Biotechnology Genome Editing in Agricultural Biotechnology Genome editing is a tool that plant breeders can use to introduce new traits into crops. Plant breeders are using genome editing to develop food crops that address the needs of a growing global population and can handle a changing environment. Genome editing allows plant breeders to make very precise changes to DNA. The scientists who developed CRISPR received a Nobel Prize for their work. Another genome editing tool, TALENs, was used to develop the first genome-edited plant to be commercially grown in the United States and sold as a food product: soybeans that produce high oleic, low linolenic oil that is a healthier alternative to partially hydrogenated oils.
[195] Advances in Genome Editing for Sustainable Agriculture — Using cutting-edge biotechnologies to improve crop yield and nutritional quality will help to keep modern agriculture sustainable. Genome editing enables breeders to introduce sequence changes at a specific locus, thus allowing the precise modulation of traits of interest of crops. Because it is simple, cost-effective, and efficient, CRISPR
[196] Editorial: Genome editing for agricultural sustainability: developments ... — Collectively, the articles in this Research Topic demonstrate the potential for genome editing to have a prominent role in improving the sustainability of agriculture, with broader implications for the global challenges of food security and nutrition.
[197] Crop bioengineering via gene editing: reshaping the future of agriculture — A new era of genome engineering initiated by the development of genome-editing technologies is allowing the alteration and targeting of specific DNA sequences to modify plant genomes efficiently, accurately, and quickly (Jaganathan et al. The CRISPR/Cas9 system was developed as a genome-editing tool in 2012 (Mali et al. Since its initial development, the CRISPR-Cas9 system has been further optimized to enhance its specificity and allow precise genome editing with minimal effects on the genome (Jaganathan et al. To generate single-nucleotide changes, which are difficult for traditional CRISPR/Cas systems, base editors are a recently developed, highly accurate, genome-editing technology that enables targeted, irreversible conversion of individual bases at desired locations (Fig. 3A) (Gaudelli et al.
[198] Gene-Editing in Agriculture: The Future of Food Security? — In agriculture, gene-editing offers the potential to create crops that are more resilient to environmental stressors, have higher nutritional content, and require fewer resources to cultivate. One of the most significant benefits of gene-editing in agriculture is the ability to enhance crop resilience. However, with gene-editing, scientists can rapidly develop crops with enhanced resistance to such conditions. Gene-editing also holds promise for improving the nutritional content of crops, which is essential for addressing malnutrition and promoting public health. While the potential benefits of gene-editing in agriculture are immense, the technology is not without its ethical considerations and regulatory challenges. By enhancing crop resilience, improving nutritional content, and reducing environmental impact, this technology has the potential to transform agriculture and ensure that we can feed the world’s growing population.
[200] Genome Editing for Global Food Security - ScienceDirect — Global food security is increasingly challenging in light of population increase, the impact of climate change on crop production, and limited land available for agricultural expansion. Here we outline how genome editing provides excellent and timely methods to optimize crop plants, and argue the urgency for societal acceptance and support.
[201] Genome editing in future crop protection: utilizing CRISPR/Cas9 to ... — Increasing population and climate change pose significant threats to global food security by imposing stresses on plants, making them more susceptible to diseases and productivity losses caused by pathogens, pests, and weeds. Traditional breeding strategies are insufficient for rapid development of new plant traits that can outpace this productivity downtrend. Modern advances in genome editing
[202] Genome-edited livestock: Ethics and social acceptance — The breeding of farm animals using genome editing should be performed after due considerations in relation to the ethical implications of animal genetic modification in society. Moreover, for animal welfare, developers should thoroughly investigate the occurrence of off-target mutations in the breeding of genome-edited animals.
[228] Genome editing and sustainable agriculture - Nature Sustainability — Genome editing and sustainable agriculture | Nature Sustainability nature The application of genome editing technology in agriculture is clearly beneficial; however, it also opens doors for a host of associated social and ethical issues, such as intellectual property rights associated with the use of the technology and the question of who benefits from such crops in terms of the stakeholders involved, such as farmers, consumers and multinational corporations. The ongoing debate on the promise of genome editing technology and its associations with other approaches in agriculture towards improving food security and ecosystem and environmental health is interesting and relevant to sustainability.
[239] Equity, Sovereignty, and Racial Justice: Beyond Access in Debates on ... — How should we talk about equity in the context of human genome editing? While sky-high costs and lack of access to potential somatic gene therapies are important to address, we also need to ask critical questions about health equity, sovereignty, and racial justice--particularly in relation to heritable genome editing, which would alter the
[240] Navigating equity in global access to genome therapy expanding access ... — Potential impediments such as countries’ lack of regulatory capacity to evaluate these advanced therapies, a shortage of manufacturing capabilities for genome therapy production, inadequate data infrastructures for the protection of sensitive genome information, health literacy deficits impeding comprehension of treatment benefits and risks, and deficient public health systems and workforce, could globally restrict patient access. A human rights-based approach to global access to sickle cell disease genome therapy underscores the importance of robust health systems and a regulatory framework to govern cell and gene therapies at the national level. To ensure global equitable access to SCD genome therapies, it is necessary to guide all phases - from research and development to regulatory approval, manufacturing, and delivery - by principles of human rights and health equity.
[241] The ethics, equity, and governance of human genome editing ... - The BMJ — Adopting a purely scientific view of human genome editing risks ignoring ethical, societal, and equity considerations, writes Sarojini Nadimpally Challenges exist around heritable gene editing, its potential medical applications, ethical implications, and the need for regulatory mechanisms in the field. In March this year I spoke at the Third International Summit on Human Genome Editing, held
[242] Defining and Achieving Health Equity in Genomic Medicine — Increase representation of underrepresented groupsResearchersPrioritize recruitment of underrepresented participants over quickly reaching recruitment goalsInvestigate research questions of special interest to diverse and underserved populationsConduct clinical genomic studies in diverse healthcare settingsIncrease community engagement to build relationships, garner trust, and address local concernsFundersEncourage higher levels of inclusion in study design and review criteria for funding opportunitiesProvide investigators adequate time and resources to engage communitiesActively monitor and support researchers in reaching recruitment targetsFacilitate equal access to genomic servicesResearchersBuild on evidence base for cost-effectiveness and clinical utility of genomic testsEngage payers to promote evidence-based coverage of genomic servicesPayersCommunicate what evidence is needed to make coverage decisions about tests and genetic counseling servicesPolicymakersExplore ways to promote access to testing for underserved groups, such as through state Medicaid policiesResearch institutions, medical centers, and medical schoolsInvest resources and make it routine for health care providers to learn about genomicsIncorporate genomics into medical school curricula, continuing medical education courses, and point of care resources, among othersConduct implementation science studies to learn how to effectively integrate genomics into the clinical care of diverse groupsBuild infrastructure outside traditional settingsFunders and institutionsSupport research that strengthens infrastructure outside traditional settingsRecruit and train minority investigators
[246] Regulatory, ethical, social, and biosafety concerns in genome-edited ... — In conclusion, while gene editing using CRISPR technology holds great promise for the horticultural industry, it is essential that regulatory, ethical, social, and biosafety concerns are carefully considered and addressed to ensure the safe and responsible development and use of genome-edited crops.
[247] (PDF) Off-target effects in CRISPR/Cas9 gene editing - ResearchGate — A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome.
[248] CRISPR-Cas9 Off-Target Effects: Challenges and Solutions — Risks of CRISPR-Cas9 Off-Target Gene Editing. An off-target gene editing by CRISPR-Cas9 could result in the introduction of new genetic mutations instead of fixing them. 6 An off-target mutation in critical genes could disrupt normal cellular activities and potentially cause adverse conditions or diseases. It could also lead to a wide array of unanticipated serious consequences, including
[249] Off-target effects in CRISPR/Cas9 gene editing - PMC - PubMed Central (PMC) — The off-target sites are often sgRNA-dependent, since Cas9 is known to tolerate up to 3 mismatches between sgRNA and genomic DNA (Fu et al., 2013; Hsu et al., 2013; Wang et al., 2016a). Some of these detection methods for off-targets prediction is applicable for other family of Cas nucleases, such as Cas12a (Cpf1), which also create DSBs on off-target sites (Kim et al., 2019). Another more popular method to detect off-target sites in cells is called GUIDE-seq (Tsai et al., 2015). Although CBE and ABE greatly reduce the classic off-target effects of CRISPR/Cas9 systems, they create new formats of off-target effects such as RNA editing and sgRNA-independent DNA editing (Grünewald et al., 2019; Jin et al., 2019; Zhou et al., 2019; Zuo et al., 2019).
[264] CRISPR Gene Therapies: Current Challenges and a Promising Future — Arguably the greatest challenge to be overcome before the widespread clinical application of CRISPR-based gene editing is mitigating the risk of off-target effects—or unintended genetic alterations at sites other than the intended target.4 Researchers have made significant progress in improving the precision of CRISPR by developing more precise Cas9 variants and optimizing guide RNA designs. But the reliance on the introduction of a DSB can also cause significant safety issues, with CRISPR gene editing leading to cell death, or large base-deletions and chromosomal disorganization with the potential to cause malignant tumors.5 A key focus has been to develop CRISPR systems that do not introduce a DSB—systems such as base editing, prime editing, and the derivatives TWIN-PE and PASTE facilitate gene editing without a DSB, from single nucleotide changes to large-scale insertions of genetic material, with huge future potential for gene therapy.6