Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo**
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Der Einfluss des pKS-Werts von ionisierbaren Lipiden auf den siRNA-Transport durch Lipidnanopartikel in vivo wurde anhand zahlreicher Modifikationen der Lipid-Kopfgruppen studiert. Dabei wurde ein Zusammenhang zwischen pKS-Wert und Stummschaltung des Maus-FVII-Gens (FVII ED50) gefunden: pKS-Werte von 6.2–6.5 erwiesen sich als optimal (siehe Diagramm). Für das wirksamste kationische Lipid betrug ED50 etwa 0.005 mg kg−1 in Mäusen und <0.03 mg kg−1 in Primaten (außer Menschen).
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Endosomal escape can be increased by optimizing the pKa values of ionizable lipids.
“Endosomal escape can be increased by optimizing the pKa values of ionizable lipids66,76–78,88,100,140.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [66]
The delivery efficacy of mRNA could be improved by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle-mRNA formulations.
“Moreover, the delivery efficacy of mRNA could be improved, for example, by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle–mRNA formulations64,66,76–78,88,97,100,114,140,141.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [66]
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The siRNAsome: A Cation‐Free and Versatile Nanostructure for siRNA and Drug Co‐delivery
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Nonviral targeted mRNA delivery: principles, progresses, and challenges
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- Authors
- Jayaraman, M., Ansell, S. M., Mui, B. L., Tam, Y. K., Chen, J., Du, X., Butler, D., Eltepu, L., Matsuda, S., Narayanannair, J. K., Rajeev, K. G., Hafez, I. M., Akinc, A., Maier, M. A., Tracy, M. A., Cullis, P. R., Madden, T. D., Manoharan, M., & Hope, M. J.
- Affiliations
- Alnylam Pharmaceuticals (United States) (US)
- AlCana Technologies Vancouver BC Canada
- University of British Columbia (CA)
- Corresponding author
- Jayaraman, Muthusamy
- Hope, Michael J.
- ORCID
- Venue
- Angewandte Chemie
- Publisher
- Wiley
- Published
- 2012-07-10
- Volume
- 124
- Issue
- 34
- Pages
- 8657-8661
- ISSN
- 0044-8249 (ISSN-L)
- 1521-3757
- OpenAlex
- W4256219020
- Cited by
- 150
- References
- 15
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 38 · 2023: 30 · 2022: 24 · 2021: 14 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 2
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Angewandte Chemie (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- siRNA, lipid nanoparticles, ionizable lipids, pKa, cationic lipids, factor VII, siRNA delivery, in vivo gene silencing, ED50
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