Evidence map›Paper›PMID 42189993›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.

Andrew L Sabol, Amanuella A Mengiste, Prashant Singh, Vedagopuram Sreekanth, Samuel J Hendel, Minh Thuan Nguyen Tran, Anton M Barybin, Santosh Chaudhary, Ra'Mal M Harris, Kristi E Liivak and 8 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Andrew L Sabol *Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Amanuella A Mengiste *Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Prashant Singh *Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.ORCID 0009-0002-8893-2373
Vedagopuram Sreekanth *Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Samuel J HendelDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Minh Thuan Nguyen TranDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Anton M BarybinDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Santosh ChaudharyBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Ra'Mal M HarrisDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Kristi E LiivakDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Zachary C SeveranceBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Cale M LociceroDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
Karishma KailassBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.ORCID 0009-0003-7052-490X
Chaiheon LeeBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Lucy Qinghua XuBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.
Vincent L ButtyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Amit ChoudharyBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.ORCID 0000-0002-8437-0150
Matthew D ShouldersDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-6511-3431

Funding

Development of platforms for sorting, production, editing of beta cellsR01DK132900 · NIDDK · BROAD INSTITUTE, INC. · PI Amit Choudhary, Neal Krishna Devaraj · 2023 to 2026
$2.6M
Leveraging Next-Generation Directed Evolution Platforms and Chemical Control of Proteostasis to Deliver Robust Biotechnologies and Illuminate Roles of Chaperone Networks in Protein EvolutionR35GM136354 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHOULDERS, MATTHEW DONALD · 2020 to 2024
$2.1M
Chemical approaches for precision genome editingR01GM137606 · NIGMS · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2021 to 2024
$1.5M
Development of synthetic gene drives using small moleculesR01GM132825 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI AKBARI, OMAR SULTAN, CHOUDHARY, AMIT · 2019 to 2022
$1.4M
Damon Runyon Cancer Research Foundation (DRCRF) DRG-2539-24DOD | ARPA | Defense Sciences Office, DARPA (DSO) N66001-17-2-4055HHS | NIH | National Cancer Institute (NCI) P30-CA14051HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK132900HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM132825HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM137606HHS | NIH | National Institute of General Medical Sciences (NIGMS) R35GM136354National Science Foundation (NSF) 2330699Natural Sciences and Engineering Research Council of Canada (NSERC) 587836-2024NIGMS NIH HHS R35 GM136354
6 · The paper itself

Abstract

Engineering CRISPR-Cas systems for improved or altered function is critical to both research and therapeutic applications. Unfortunately, most optimization, especially directed evolution in bacterial hosts, fails to capture the functional requirements of the complex mammalian cellular milieu, where activity is usually required. Robust strategies to enable continuous directed evolution of genome-targeting agents directly in human cells remain lacking. Here, we introduce CRISPR-MACE (Mammalian cell-enabled Adenovirus-assisted Continuous Evolution) as a foundational technology to address this need. CRISPR-MACE integrates virus-based continuous evolution with anti-CRISPR-based tunable selection to generate

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDirected Molecular EvolutionAdenoviridaeHEK293 CellsHumansMutationStreptococcus pyogenesanti-CRISPRCRISPR-Cas9directed evolutionprotein engineeringsynthetic biology

Identifiers

PMID42189993
PMCPMC13229284

What Socratic holds

Textmetadata
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 Socratic graph.