Evidence map›Paper›PMID 41851306›Full record

ArticleNature biotechnology2026

Precise, minimally evolved adenine base editors generated through mutation reversion analysis.

Mallory Evanoff, Sanjana Korpal, Zachary D Krill, Quinn T Cowan, Alexis C Komor

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Mallory EvanoffDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-6399-7731
Sanjana KorpalDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Zachary D KrillDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0003-8301-6664
Quinn T CowanDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
Alexis C KomorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA. akomor@ucsd.edu.ORCID http://orcid.org/0000-0001-5043-0998

Funding

GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Supplement to R35 "Development and Application of New Genome Editing Tools for the Functional Investigation of Genetic Variants of Uncertain Significance"R35GM138317 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alexis C. Komor · 2020 to 2026
$2.8M
UC San Diego Genetics Training ProgramT32GM145427 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRUCE A HAMILTON · 2022 to 2026
$2.6M
NIGMS NIH HHS R35 GM138317NIGMS NIH HHS T32 GM007240NIGMS NIH HHS T32 GM008326NIGMS NIH HHS T32 GM145427U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 2R35GM138317U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32 GM007240-41
6 · The paper itself

Abstract

The initial development of adenine base editors (ABEs), which facilitate A•T to G•C base pair changes in the genome, used directed evolution to install 14 mutations into the wild-type deaminase TadA, producing the first-of-its-kind editor ABE7.10. Here we study the installed mutations' impacts on TadA fitness using comprehensive reversion analysis and apply our results to engineer more efficient, precise editors. By measuring activity in both human and Escherichia coli host systems, we categorize mutations as critical, dispensable or host dependent. We show that up to five mutations can be reverted back to wild type, generating minimally evolved ABEs (ME-ABEs). ME-ABEs show narrow editing windows (similar to that of ABE7.10) and enhanced on-target editing (matching activities of the high-activity editor variants ABE8e and ABE8.20 in most sequence contexts) and exhibit low levels of guide-RNA-dependent and guide-RNA-independent off-target activity. ME-ABEs efficiently target six sites of clinical interest that had previously proved challenging to edit with ABE7.10, ABE8e or ABE8.20.

Identifiers

PMID41851306
PMCPMC13470211

What OpenQuestion holds

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Registered trials

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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.