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Cited by 1,349RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryRNA and protein synthesis mechanisms

Drug delivery systems for RNA therapeutics

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Paunovska, Kalina, Loughrey, David, Dahlman, James E.·2022·Nature Reviews Genetics
DOI 10.1038/s41576-021-00439-4PMC PMC8724758
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Abstract

RNA-based gene therapy requires therapeutic RNA to function inside target cells without eliciting unwanted immune responses. RNA can be ferried into cells using non-viral drug delivery systems, which circumvent the limitations of viral delivery vectors. Here, we review the growing number of RNA therapeutic classes, their molecular mechanisms of action, and the design considerations for their respective delivery platforms. We describe polymer-based, lipid-based, and conjugate-based drug delivery systems, differentiating between those that passively and those that actively target specific cell types. Finally, we describe the path from preclinical drug delivery research to clinical approval, highlighting opportunities to improve the efficiency with which new drug delivery systems are discovered.

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  • Viral delivery platforms can be limited by pre-existing viral immunity, transgene size constraints, undesired vector integration, and adverse events related to the viral vector.

    “Although viral vectors are a promising approach to deliver gene editing technology to the CNS, viral delivery platforms can be limited by pre-existing viral immunity, transgene size constraints, undesired vector integration, and adverse events related to the viral vector (10–12).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [10]

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Cited by

Sorted by citations

Authors
Paunovska, K., Loughrey, D., & Dahlman, J. E.
Affiliations
Georgia Institute of Technology (US)
Corresponding author
Dahlman, James E.
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2022-01-04
Volume
23
Issue
5
Pages
265-280
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/s41576-021-00439-4
PMC
PMC8724758
OpenAlex
W4205824800
Cited by
1,349
References
55
Citations by year
2026: 274 · 2025: 357 · 2024: 378 · 2023: 258 · 2022: 81 · 2012: 1
FWCI
27.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Georgia Institute of Technology
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RNA therapeutics, RNA delivery systems, non-viral gene delivery, gene therapy, active targeting, passive targeting, preclinical to clinical translation
MeSH terms
Genetic Vectors, Genetic Therapy, Drug Delivery Systems, RNA, Small Interfering

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