The Future of Tissue-Targeted Lipid Nanoparticle-Mediated Nucleic Acid Delivery
Open accessAbstract
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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The highly modular nature of LNPs allows them to be optimized for organ- and cell type-specific delivery following systemic administration.
“Furthermore, the highly modular nature of LNPs allows them to be optimized for organ- and cell type-specific delivery following systemic administration.23–25”
From Predictive High-Throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood–Brain Barrier Transfection and Crossing (2024) · cites this paper as [24]
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Cited by
Sorted by citations
Han, E. L., Padilla, M. S., Palanki, R., Kim, D., Mrksich, K., Li, J. J., Tang, S., Yoon, I.-C., & Mitchell, M. J. (2024) · Nano Letters · doi:10.1021/acs.nanolett.3c03509 · Cited by 72 · see citing works
- 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)
- PMC
- PMC9322927
- 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
- gold
- doi.org
- Licence
- 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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