ArticleCell chemical biology2019
A Bump-Hole Approach for Directed RNA Editing.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Clickable RNA via 4'-Bioconjugate chemistry · 2025Article
- Phylogenetic and structural analysis of Hydra ADAR.Archives of biochemistry and biophysics · 2025Article
- Structural analysis of human ADAR2-RNA complexes by X-ray crystallography.Methods in enzymology · 2025Article
- Site-specific regulation of RNA editing with ribose-modified nucleoside analogs in ADAR guide strands.Nucleic acids research · 2024Article
- RNA editing enzymes: structure, biological functions and applications.Cell & bioscience · 2024Review
- Engineered deaminases as a key component of DNA and RNA editing tools.Molecular therapy. Nucleic acids · 2023Review
- RNA editing: Expanding the potential of RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Selective Inhibition of ADAR1 Using 8-Azanebularine-Modified RNA Duplexes.Biochemistry · 2023Article
- Site-directed A → I RNA editing as a therapeutic tool: moving beyond genetic mutations.RNA (New York, N.Y.) · 2023Article
- Nucleoside analogs in ADAR guide strands targeting 5'-UA̲ sites.RSC chemical biology · 2023Article
- ADAR activation by inducing a syn conformation at guanosine adjacent to an editing site.Nucleic acids research · 2022Article
- Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs.Nature biotechnology · 2022Article
- Article
- Site-directed RNA editing: recent advances and open challenges.RNA biology · 2021Review
- Rational Design of RNA Editing Guide Strands: Cytidine Analogs at the Orphan Position.Journal of the American Chemical Society · 2021Article
- In Vivo Repair of a Protein Underlying a Neurological Disorder by Programmable RNA Editing.Cell reports · 2020Article
- Suppression of Nonsense Mutations by New Emerging Technologies.International journal of molecular sciences · 2020Review
- RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells.Nucleic acids research · 2019Article
- Identification of Adenosine-to-Inosine RNA Editing with Acrylonitrile Reagents.Organic letters · 2019Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Molecules capable of directing changes to nucleic acid sequences are powerful tools for molecular biology and promising candidates for the therapeutic correction of disease-causing mutations. However, unwanted reactions at off-target sites complicate their use. Here we report selective combinations of mutant editing enzyme and directing oligonucleotide. Mutations in human ADAR2 (adenosine deaminase acting on RNA 2) that introduce aromatic amino acids at position 488 reduce background RNA editing. This residue is juxtaposed to the nucleobase that pairs with the editing site adenine, suggesting a steric clash for the bulky mutants. Replacing this nucleobase with a hydrogen atom removes the clash and restores editing activity. A crystal structure of the E488Y mutant bound to abasic site-containing RNA shows the accommodation of the tyrosine side chain. Finally, we demonstrate directed RNA editing in vitro and in human cells using mutant ADAR2 proteins and modified guide RNAs with reduced off-target activity.
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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 OpenQuestion graph.