ArticleNucleic acids research2024
Rational design of base, sugar and backbone modifications improves ADAR-mediated RNA editing.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Article
- Targeting intracellular mRNA mJournal of advanced research · 2026Review
- Evolution of Engineered ADAR-Based RNA Editing Systems.International journal of molecular sciences · 2026Review
- RNA editing for the treatment of alpha-1 antitrypsin deficiency.Nucleic acids research · 2026Article
- m6A-Modified Nucleotide Bases Improve Translation of In Vitro-Transcribed Chimeric Antigen Receptor (CAR) mRNA in T Cells.International journal of molecular sciences · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Clickable RNA via 4'-Bioconjugate chemistry · 2025Article
- Discovery and Tuning of RNA Editing Guides via High-Throughput Screening and Chemical Modification.Chembiochem : a European journal of chemical biology · 2025Article
- Control of ADAR2 Dimerization and RNA Editing Efficiency by Site-Specific 2'-Fluoro Modification of Guide RNAs.ACS chemical biology · 2025Article
- Article
- ADARs: pleiotropy in function, versatility in application.Nucleic acids research · 2025Review
- Emerging clinical applications of ADAR based RNA editing.Stem cells translational medicine · 2025Review
- Zα and Zβ Localize ADAR1 to Flipons That Modulate Innate Immunity, Alternative Splicing, and Nonsynonymous RNA Editing.International journal of molecular sciences · 2025Review
- Review
- Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.Nature communications · 2025Article
- Paradigm shift in obesity treatment: an extensive review of current pipeline agents.Turkish journal of medical sciences · 2025Review
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Authors and funding
28 authors.
Funding
Abstract
AIMers are short, chemically modified oligonucleotides that induce A-to-I RNA editing through interaction with endogenous adenosine deaminases acting on RNA (ADAR) enzymes. Here, we describe the development of new AIMer designs with base, sugar and backbone modifications that improve RNA editing efficiency over our previous design. AIMers incorporating a novel pattern of backbone and 2' sugar modifications support enhanced editing efficiency across multiple sequences. Further efficiency gains were achieved through incorporation of an N-3-uridine (N3U), in place of cytidine (C), in the 'orphan base' position opposite the edit site. Molecular modeling suggests that N3U might enhance ADAR catalytic activity by stabilizing the AIMer-ADAR interaction and potentially reducing the energy required to flip the target base into the active site. Supporting this hypothesis, AIMers containing N3U consistently enhanced RNA editing over those containing C across multiple target sequences and multiple nearest neighbor sequence combinations. AIMers combining N3U and the novel pattern of 2' sugar chemistry and backbone modifications improved RNA editing both in vitro and in vivo. We provide detailed N3U synthesis methods and, for the first time, explore the impact of N3U and its analogs on ADAR-mediated RNA editing efficiency and targetable sequence space.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.