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Cited by 171RNA regulation and diseaseRNA modifications and cancerCRISPR and Genetic Engineering

RNA editing: Expanding the potential of RNA therapeutics

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Booth, Brian J., Nourreddine, Sami, Katrekar, Dhruva, Savva, Yiannis, Bose, Debojit, Long, Thomas J., Huss, David J., Mali, Prashant·2023·Molecular Therapy
DOI 10.1016/j.ymthe.2023.01.005PMC PMC9824937
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Abstract

RNA therapeutics have had a tremendous impact on medicine, recently exemplified by the rapid development and deployment of mRNA vaccines to combat the COVID-19 pandemic. In addition, RNA-targeting drugs have been developed for diseases with significant unmet medical needs through selective mRNA knockdown or modulation of pre-mRNA splicing. Recently, RNA editing, particularly antisense RNA-guided adenosine deaminase acting on RNA (ADAR)-based programmable A-to-I editing, has emerged as a powerful tool to manipulate RNA to enable correction of disease-causing mutations and modulate gene expression and protein function. Beyond correcting pathogenic mutations, the technology is particularly well suited for therapeutic applications that require a transient pharmacodynamic effect, such as the treatment of acute pain, obesity, viral infection, and inflammation, where it would be undesirable to introduce permanent alterations to the genome. Furthermore, transient modulation of protein function, such as altering the active sites of enzymes or the interface of protein-protein interactions, opens the door to therapeutic avenues ranging from regenerative medicine to oncology. These emerging RNA-editing-based toolsets are poised to broadly impact biotechnology and therapeutic applications. Here, we review the emerging field of therapeutic RNA editing, highlight recent laboratory advancements, and discuss the key challenges on the path to clinical development.

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Cited by

Sorted by citations

Authors
Booth, B. J., Nourreddine, S., Katrekar, D., Savva, Y., Bose, D., Long, T. J., Huss, D. J., & Mali, P.
Affiliations
University of California San Diego (US)
Corresponding author
  • Huss, David J.
  • Mali, Prashant
ORCID
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2023-06
Volume
31
Issue
6
Pages
1533-1549
ISSN
1525-0016 (ISSN-L)
DOI
10.1016/j.ymthe.2023.01.005
PMC
PMC9824937
OpenAlex
W4313680674
Cited by
171
References
7
Citations by year
2026: 42 · 2025: 61 · 2024: 57 · 2023: 11
FWCI
4.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • California Institute for Regenerative Medicine (EDUC4-12804)
  • DOD (W81XWH-22-1-0401)
  • NIH (OT2OD032742, R01GM123313)
  • University of California, San Diego
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
RNA editing, A-to-I RNA editing, ADAR, RNA therapeutics, mRNA vaccines, pre-mRNA splicing, mRNA knockdown, protein function modulation
MeSH terms
COVID-19, Adenosine Deaminase, Humans, RNA, RNA-Binding Proteins, RNA Editing, Pandemics

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