Evidence map›Paper›PMID 39533106›Full record

ArticleNature biotechnology2025

Multimodal scanning of genetic variants with base and prime editing.

Olivier Belli, Kyriaki Karava, Rick Farouni, Randall J Platt

Abstract read
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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

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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

4 authors.

Olivier Belli *Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-7711-9312
Kyriaki Karava *Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID http://orcid.org/0009-0006-5383-1723
Rick FarouniDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3454-2946
Randall J PlattDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. rplatt@ethz.ch.ORCID http://orcid.org/0000-0002-2914-7052

Funding

Verein fur Krebsforschung (Association for Cancer Research) KFS-5736-02-2023
6 · The paper itself

Abstract

Mutational scanning connects genetic variants to phenotype, enabling the interrogation of protein functions, interactions and variant pathogenicity. However, current methodologies cannot efficiently engineer customizable sets of diverse genetic variants in endogenous loci across cellular contexts in high throughput. Here, we combine cytosine and adenine base editors and a prime editor to assess the pathogenicity of a broad spectrum of variants in the epithelial growth factor receptor gene (EGFR). Using pooled base editing and prime editing guide RNA libraries, we install tens of thousands of variants spanning the full coding sequence of EGFR in multiple cell lines and assess the role of these variants in tumorigenesis and resistance to tyrosine kinase inhibitors. Our EGFR variant scan identifies important hits, supporting the robustness of the approach and revealing underappreciated routes to EGFR activation and drug response. We anticipate that multimodal precision mutational scanning can be applied broadly to characterize genetic variation in any genetic element of interest at high and single-nucleotide resolution.

Indexed as

ErbB ReceptorsGene EditingGenetic VariationCell Line, TumorHumansMutationEGFR protein, humanErbB Receptors

Identifiers

PMID39533106
PMCPMC12440817

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.