Cited by 150RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo**

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Jayaraman, Muthusamy, Ansell, Steven M., Mui, Barbara L., Tam, Ying K., Chen, Jianxin, Du, Xinyao, Butler, David, Eltepu, Laxman +11 more·2012·Angewandte Chemie

Abstract

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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  1. N. Demaurex, News Physiol. Sci. 2002, 17, 1 -5.

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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.
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
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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