Cited by 22RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

Enhancing siRNA delivery by employing lipid nanoparticles

Hope, Michael J·2014·Therapeutic Delivery

Abstract

For several decades extensive research has been conducted into the development of fusogenic lipid nanoparticles (LNPs) capable of introducing large, charged molecules into the cytoplasm of target cells. The majority of this work has focused on cationic LNPs encapsulating nucleic acids ranging from small oligonucleotides to large plasmid constructs thousands of bases long. However, since the introduction of siRNA payloads this quest for a non-viral, intracellular delivery systems has advanced significantly. Of particular importance was the demonstration that LNPs containing ionizable, dialkylamino lipids, enable potent hepatic gene silencing across species including humans. This review focuses on the evolution of this delivery system, summarizes the promising data now emerging from clinical trials and considers future directions for the platform.

Integrity signals

Registry

Crossref · 10.4155/tde.14.37

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71 of 71 references verified0 citation errors · 0 not checkable

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  • At blood pH, LNPs exhibit a net neutral surface charge but become positively charged in acidified endosomes following ApoE-mediated endocytosis by hepatocytes in vivo, resulting in endosome disruption and release of mRNA into the cytoplasm.

    “At blood pH, LNPs exhibit a net neutral surface charge but become positively charged in acidified endosomes following ApoE-mediated endocytosis by hepatocytes in vivo, resulting in endosome disruption and release of mRNA into the cytoplasm.28,41,45”
  • The values obtained in nonhuman primates following intravenous administration of a reasonable dose of mRNA encapsulated in LNPs designed for hepatic delivery of nucleic acid therapeutics are very much in line with the clinical EPO values.

    “These values are very much in line with those we obtained in nonhuman primates following intravenous administration of a reasonable dose of mRNA encapsulated in LNPs designed for hepatic delivery of nucleic acid therapeutics.41”

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Authors
Hope, M. J.
Affiliations
Acuitas Therapeutics (Canada) (CA)
Corresponding author
Hope, Michael J
Venue
Therapeutic Delivery
Published
2014-06
Volume
5
Issue
6
Pages
663-673
ISSN
  • 2041-5990 (ISSN-L)
  • 2041-6008
OpenAlex
W2113709410
Cited by
22
References
71
Citations by year
2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3
FWCI
0.28
Type
journal article
Language
en
Open access
closed
Locations
  • Therapeutic Delivery (publishedVersion)
  • PubMed (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 delivery, lipid nanoparticles, ionizable lipids, non-viral gene delivery, clinical trials, nucleic acid encapsulation
MeSH terms
Animals, Clinical Trials as Topic, Humans, Lipids, Drug Delivery Systems, Gene Silencing, RNA, Small Interfering, Nanoparticles

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