Angewandte Chemie International Edition · 2012 · 1.2K citations · 12 references
PharmacyPharmaceuticsPharmacologyDrug DeliveryGene DeliveryNanoparticle Drug DeliveryLipid ChemistryLipid TransportLipid-based Drug Delivery SystemsLipid-based NanoparticlesNanocarriers For TherapeuticsNanoparticle DesignIonizable Lipid SystemsLipid NanocarriersLipid NanomaterialsLipid Nanoparticle Delivery SystemsLipid Nanoparticle ToxicityLipid NanoparticlesPharmacokinetics Of NanocarriersTranscriptional Gene Silencing
Special (lipid) delivery: The role of the ionizable lipid pK(a) in the in vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.5. The most potent cationic lipid from this study has ED(50) levels around 0.005 mg kg(-1) in mice and less than 0.03 mg kg(-1) in non-human primates.
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Rational design of cationic lipids for siRNA delivery
Sean C. Semple, Akin Akinc, Jianxin Chen et al. · Nature Biotechnology · 2010 · 1.8K citations
RNAi-mediated gene silencing in non-human primates
Tracy Zimmermann, Amy C. H. Lee, Akin Akinc et al. · Nature · 2006 · 1.3K citations
Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms
Akin Akinc, William Querbes, Soma De et al. · Molecular Therapy · 2010 · 1.2K citations · Full text