Evidence map›Paper›PMID 39562753›Full record

ArticleNature methods2025

A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening.

Ann Cirincione, Danny Simpson, Weihao Yan, Ryan McNulty, Purnima Ravisankar, Sabrina C Solley, Jun Yan, Fabian Lim, Emma K Farley, Mona Singh and 1 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Ann Cirincione *Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0003-0475-5331
Danny Simpson *Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-9690-3527
Weihao YanDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0009-0000-2509-1816
Ryan McNultyLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-6727-7408
Purnima RavisankarLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-7799-4558
Sabrina C SolleyDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-2356-5608
Jun YanDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0009-0005-9139-3966
Fabian LimDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5628-7707
Emma K FarleyDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-9241-247X
Mona SinghLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Britt AdamsonLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. badamson@princeton.edu.ORCID http://orcid.org/0000-0002-9451-5819

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI STEVEN ZHENG · 1997 to 2026
$94.5M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007388 · NIGMS · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 1985 to 2022
$27.4M
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Quantitavie and Computational Biology Graduate ProgramT32HG003284 · NHGRI · PRINCETON UNIVERSITY · PI Joshua Michael Akey, Stanislav Y. Shvartsman · 2004 to 2026
$9.9M
Predicting and analyzing variation in cellular interactomesR01GM076275 · NIGMS · PRINCETON UNIVERSITY · PI SINGH, MONA · 2006 to 2022
$4.0M
Mapping the DNA damage response in human cells with high-resolution functional genomicsR35GM138167 · NIGMS · PRINCETON UNIVERSITY · PI Brittany S. Adamson · 2020 to 2026
$2.4M
Characterizing the interpretation and generation of Erk signaling dynamics using high-throughput geneticsF31HD113443 · NICHD · PRINCETON UNIVERSITY · PI Sabrina Solley · 2024 to 2026
$101k
National Science Foundation (NSF) 2239957National Science Foundation (NSF) DGE-2039656NCI NIH HHS P30 CA072720NHGRI NIH HHS RM1 HG009490NHGRI NIH HHS T32 HG003284NICHD NIH HHS F31 HD113443NIGMS NIH HHS R01 GM076275NIGMS NIH HHS R35 GM138167NIGMS NIH HHS T32 GM007388U.S. Department of Health & Human Services | National Institutes of Health (NIH) F31HD113443U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30CA072720U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01-GM076275U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM138167U.S. Department of Health & Human Services | National Institutes of Health (NIH) RM1HG009490U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM007388U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32HG003284
6 · The paper itself

Abstract

Prime editing installs precise edits into the genome with minimal unwanted byproducts, but low and variable editing efficiencies have complicated application of the approach to high-throughput functional genomics. Here we assembled a prime editing platform capable of high-efficiency substitution editing suitable for functional interrogation of small genetic variants. We benchmarked this platform for pooled, loss-of-function screening using a library of ~240,000 engineered prime editing guide RNAs (epegRNAs) targeting ~17,000 codons with 1-3 bp substitutions. Comparing the abundance of these epegRNAs across screen samples identified negative selection phenotypes for 7,996 nonsense mutations targeted to 1,149 essential genes and for synonymous mutations that disrupted splice site motifs at 3' exon boundaries. Rigorous evaluation of codon-matched controls demonstrated that these phenotypes were highly specific to the intended edit. Altogether, we established a prime editing approach for multiplexed, functional characterization of genetic variants with simple readouts.

Indexed as

Gene EditingCRISPR-Cas SystemsHumansRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39562753
PMCPMC11725502

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.