Cited by 109RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

The Future of Tissue-Targeted Lipid Nanoparticle-Mediated Nucleic Acid Delivery

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Kularatne, Ruvanthi N., Crist, Rachael M., Stern, Stephan T.·2022·Pharmaceuticals

Abstract

The earliest example of in vivo expression of exogenous mRNA is by direct intramuscular injection in mice without the aid of a delivery vehicle. The current state of the art for therapeutic nucleic acid delivery is lipid nanoparticles (LNP), which are composed of cholesterol, a helper lipid, a PEGylated lipid and an ionizable amine-containing lipid. The liver is the primary organ of LNP accumulation following intravenous administration and is also observed to varying degrees following intramuscular and subcutaneous routes. Delivery of nucleic acid to hepatocytes by LNP has therapeutic potential, but there are many disease indications that would benefit from non-hepatic LNP tissue and cell population targeting, such as cancer, and neurological, cardiovascular and infectious diseases. This review will concentrate on the current efforts to develop the next generation of tissue-targeted LNP constructs for therapeutic nucleic acids.

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Cited by

Sorted by citations

Authors
Kularatne, R. N., Crist, R. M., & Stern, S. T.
Affiliations
  • Frederick National Laboratory for Cancer Research (US)
  • Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21702, USA
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2022-07-20
Volume
15
Issue
7
Pages
897
ISSN
1424-8247 (ISSN-L)
OpenAlex
W4286500740
Cited by
109
References
13
Citations by year
2026: 21 · 2025: 41 · 2024: 26 · 2023: 17 · 2022: 4
FWCI
2.29
Type
journal article
Language
en
Open access
Locations
  • Pharmaceuticals (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Cancer Institute, National Institutes of Health (75N91019D00024)
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
lipid nanoparticles, nucleic acid delivery, mRNA therapeutics, liver targeting, intramuscular injection, helper lipids, ionizable lipids, PEGylated lipids, cancer gene therapy, neurological disorders, cardiovascular disease, infectious diseases

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