The DOI matches its Crossref record; 105 of the 105 references it cites were found in a registry or an index.
Overcoming cellular barriers for RNA therapeutics
Abstract
RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs), antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR-Cas9, have great potential to target a large part of the currently undruggable genes and gene products and to generate entirely new therapeutic paradigms in disease, ranging from cancer to pandemic influenza to Alzheimer's disease. However, for these RNA modalities to reach their full potential, they first need to overcome a billion years of evolutionary defenses that have kept RNAs on the outside of cells from invading the inside of cells. Overcoming the lipid bilayer to deliver RNA into cells has remained the major problem to solve for widespread development of RNA therapeutics, but recent chemistry advances have begun to penetrate this evolutionary armor.
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In the citing paper
“As an emerging programmable gene interference technique, siRNA offers high specificity and flexibility in targeting the diseased human genome [236].”
From Emerging role of exosomes in cancer therapy: progress and challenges (2025) · cites this paper as [236]
In the citing paper
“Many obstacles still exist despite the rise in studies on delivery platforms, including toxicity and the precise distribution of mRNA to extrahepatic organs [13, 14].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [13]
In the citing paper
“Independent of the administration route, several evolutionary barriers are designed to prevent any intrusion of foreign nucleic acids and thus limit the delivery of exogenous mRNA [74].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [74]
In the citing paper
“For instance, RNA interference (RNAi) technology enables the downregulation of disease related genes and protein expression; mRNA mediates the expression and supplementation of therapeutic proteins; the CRISPR gene editing system facilitates gene engineering in vivo or through cell engineering ex vivo.[6, 9, 11, 17–20]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [19]
In the citing paper
“For instance, RNA interference (RNAi) technology enables the downregulation of disease related genes and protein expression; mRNA mediates the expression and supplementation of therapeutic proteins; the CRISPR gene editing system facilitates gene engineering in vivo or through cell engineering ex vivo.[6, 9, 11, 17–20]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [19]
In the citing paper
“For instance, RNA interference (RNAi) technology enables the downregulation of disease related genes and protein expression; mRNA mediates the expression and supplementation of therapeutic proteins; the CRISPR gene editing system facilitates gene engineering in vivo or through cell engineering ex vivo.[6, 9, 11, 17–20]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [19]
In the citing paper
“With the development of chemical modifications on RNA molecules, modified siRNA are reported to remain intact for long durations under circulation, which provides the possibility of delivering siRNA without the shielding of nanoparticles.[19, 75, 76]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [19]
Citations
Cites
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Multiplex Genome Engineering Using CRISPR/Cas Systems
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Flagged first, then by citations
Research works printed but not linked: 2
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Cited by
Sorted by citations
Noncoding RNA therapeutics—Challenges and potential solutions
Winkle, M., El-Daly, S. M., Fabbri, M., & Calin, G. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00219-z · Cited by 1,551
The current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
Crooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841
mRNA-based therapeutics: powerful and versatile tools to combat diseases
Qin, S., Tang, X., Chen, Y., Chen, K., Fan, N., Xiao, W., Zheng, Q., Li, G., Teng, Y., Wu, M., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01007-w · Cited by 852
Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts
Stewart, M. P., Langer, R., & Jensen, K. F. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00678 · Cited by 767
Metadata
- Authors
- Dowdy, S. F.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Dowdy, Steven F
- ORCID
- Dowdy, Steven F
- Venue
- Nature Biotechnology
- Published
- 2017-02-27
- Volume
- 35
- Issue
- 3
- Pages
- 222-229
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2594133976
- Cited by
- 1,139
- References
- 105
- Citations by year
- 2026: 103 · 2025: 130 · 2024: 147 · 2023: 133 · 2022: 130 · 2021: 141 · 2020: 104 · 2019: 88 · 2018: 120 · 2017: 41
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Biotechnology (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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- RNA therapeutics, RNA delivery, lipid bilayers, siRNA, microRNA, antisense oligonucleotides, aptamers, synthetic mRNA, CRISPR/Cas9
- MeSH terms
- RNAi Therapeutics, Animals, Cell Membrane, Humans, RNA, RNA Interference, Nanocapsules, Molecular Targeted Therapy
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