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ContactSeek uses AlphaFold3 contact predictions to improve base-editor specificity

ContactSeek combines experimentally mapped off-target sites with AlphaFold3 contact probabilities to identify specificity-determining residues. The authors engineered adenine and cytosine base-editor variants and validated improved specificity with targeted sequencing, genome-wide profiling, R-loop assays and RNA sequencing.

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Stable ID
science-2026-contactseek-base-editor-specificity
Revision
science-2026-contactseek-base-editor-specificity.v1
Field
Biology and Biotechnology · AI-assisted genome editing
Evidence
Tier 2 · Peer reviewed: Yes
Record state
Current · Peer-reviewed experimental result
Last checked

AI role

AlphaFold3 predictions are a substantive part of the ContactSeek method. The authors combined those predictions with experimentally measured off-target signals and laboratory validation; the article does not present model output alone as proof.

Record details

Problem or result
Finding mutations that reduce CRISPR base-editor off-target activity without sacrificing useful on-target editing
Authors
Haowei Meng, Zhixin Lei, Yongchang Yan, Liren Wang, Chengqi Yi et al.
Institutions
Peking University, East China Normal University, AI for Science Institute and collaborators
Result date
Published July 22, 2026

Why it matters

The work turns a structure-prediction model into an experimentally tested guide for engineering more selective genome editors, addressing a central safety constraint in base editing.

Limits

The reported editors were evaluated in laboratory systems, including human cells, rather than in a clinical trial. AlphaFold3 ranked candidate contact changes, but experiments established the editing outcomes. Generality beyond the tested Cas9, Cas12a and deaminase systems remains to be shown.

Sources

  1. Primary: Nature, Precise DNA base editing using AlphaFold3-based contact modelling
  2. Primary: ContactSeek v1.0.0 archived code

Correction and revision history

  1. 2026-07-23 — Added after checking the final Nature article, peer-review record, released code, experimental validation and nonclinical scope.

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