Evidence map›Paper›PMID 41413244›Full record

ArticleNature biotechnology2025

Engineered base editors with reduced bystander editing through directed evolution.

Ramiro M Perrotta, Svenja Vinke, Raphaël Ferreira, Michaël Moret, Ahmed Mahas, Anush Chiappino-Pepe, Lisa M Riedmayr, Anna-Thérèse Mehra, Louisa S Lehmann, George M Church

Abstract read
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In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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

10 authors.

Ramiro M Perrotta *Department of Genetics, Harvard Medical School, Boston, MA, USA. Ramiro_perrotta@hms.harvard.edu.ORCID http://orcid.org/0000-0001-9072-2215
Svenja Vinke *Department of Genetics, Harvard Medical School, Boston, MA, USA.
Raphaël Ferreira *Department of Genetics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9881-6232
Michaël MoretDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8672-3386
Ahmed MahasDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1572-2383
Anush Chiappino-PepeDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3993-907X
Lisa M RiedmayrDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Anna-Thérèse MehraDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Louisa S LehmannDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0001-6232-9969

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Base editors enable precise genome modification but are constrained by bystander edits that limit their applicability. Existing strategies to enhance precision often compromise efficiency and remain highly sequence dependent. Here we present a parallel engineering approach that optimizes both guide RNAs and the deaminase enzyme to minimize bystander editing without sacrificing activity. We designed a library of 3'-extended guide RNAs and identified context-dependent variants that improved specificity. Using a precision-driven phage-assisted evolution system and protein language models, we evolved adenine base editor variants two- to threefold more precise than adenine base editor ABE8e while maintaining high efficiency across a library of thousands of human pathogenic contexts in vitro. Our findings establish a scalable framework for precision engineering of base editors, addressing a major challenge in genome editing.

Identifiers

PMID41413244

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.