Evidence map›Paper›PMID 41415442›Full record

ArticlebioRxiv : the preprint server for biology2025

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

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

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Andrew L SabolContributed equally to this work.
Amanuella A MengisteContributed equally to this work.
Vedagopuram SreekanthContributed equally to this work.
Prashant SinghContributed equally to this work.
Samuel J HendelDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Minh Thuan Nguyen TranDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Anton M BarybinDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Santosh ChaudharyBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Ra'Mal M HarrisDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Kristi LiivakDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Zachary C SeveranceBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Cale M LociceroDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Karishma KailassBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Chaiheon LeeBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Lucy Qinghua XuBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Vincent L ButtyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Amit ChoudharyBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Matthew D ShouldersDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NILES, JACQUIN C · 1985 to 2020
$25.6M
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
NCI NIH HHS P30 CA014051NIDDK NIH HHS R01 DK132900NIEHS NIH HHS P30 ES002109NIGMS NIH HHS R01 GM132825NIGMS NIH HHS R01 GM137606NIGMS NIH HHS R35 GM136354
6 · The paper itself

Abstract

Engineering CRISPR-Cas systems for improved or altered function is central 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 novel

Identifiers

PMID41415442
PMCPMC12710652

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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.