Evidence map›Paper›PMID 39388570›Full record

ArticleScience (New York, N.Y.)2024

Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes.

Xi Dawn Chen, Zeyu Chen, George Wythes, Yifan Zhang, Benno C Orr, Gary Sun, Yu-Kai Chao, Andrea Navarro Torres, Ka Thao, Mounica Vallurupalli and 6 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. 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
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025
    Review
  18. Review
  19. Article
  20. Review
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

16 authors.

Xi Dawn Chen *Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-8127-6014
Zeyu Chen *Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
George WythesGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0009-0007-2104-8870
Yifan ZhangGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0003-0484-9418
Benno C OrrGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-7231-4488
Gary SunDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.ORCID 0009-0008-6910-0161
Yu-Kai ChaoGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-9440-6746
Andrea Navarro TorresGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0009-0008-9497-7395
Ka ThaoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.ORCID 0009-0004-5315-6233
Mounica VallurupalliCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0002-1995-5283
Jing SunGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-9103-0747
Mehdi BorjiGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0009-0002-7023-434X
Emre TkacikSystems, Synthetic, and Quantitative Biology PhD Program, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-8274-1248
Haiqi ChenCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-7179-3229
Bradley E BernsteinGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0002-5726-6278
Fei ChenGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0003-2308-3649

Funding

Training Program in Molecular HematologyT32HL116324 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NANCY BERLINER · 2013 to 2026
$7.4M
COVID19 Slide-seqR01HG010647 · NHGRI · BROAD INSTITUTE, INC. · PI Fei Chen, Evan Z Macosko · 2019 to 2026
$6.0M
Epigenetic plasticity in tumor initiation and evolutionDP1CA216873 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BERNSTEIN, BRADLEY EVAN · 2016 to 2020
$5.9M
Characterizing glioma heterogeneity with novel multiplexed nanoscale imaging technologiesDP5OD024583 · OD · BROAD INSTITUTE, INC. · PI CHEN, FEI · 2017 to 2021
$2.2M
Multiplexed Locus-Specific Hypermutation for Functional Characterization of the Coding and Noncoding GenomeR01HG013336 · NHGRI · BROAD INSTITUTE, INC. · PI Fei Chen · 2025 to 2026
$1.4M
Investigating molecular mechanism of immune response during cancer progressionK00CA234842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, ZEYU · 2021 to 2024
$370k
Investigating molecular mechanism of T cell exhaustion in chronic infection and tumor microenvironmentF99CA234842 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CHEN, ZEYU · 2018 to 2019
$78k
NCI NIH HHS DP1 CA216873NCI NIH HHS F99 CA234842NCI NIH HHS K00 CA234842NHGRI NIH HHS R01 HG010647NHGRI NIH HHS R01 HG013336NHLBI NIH HHS T32 HL116324NIH HHS DP5 OD024583
6 · The paper itself

Abstract

Deciphering the context-specific relationship between sequence and function is a major challenge in genomics. Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited. Here we present a programmable platform for long-range, locus-specific hypermutation called helicase-assisted continuous editing (HACE). HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large (>1000-base pair) genomic intervals. We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1 (MEK1) that confer kinase inhibitor resistance, to dissect the impact of individual variants in splicing factor 3B subunit 1 (SF3B1)-dependent missplicing, and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69. HACE provides a powerful tool for investigating coding and noncoding variants, uncovering combinatorial sequence-to-function relationships, and evolving new biological functions.

Indexed as

CRISPR-Cas SystemsDNA HelicasesGene EditingMutagenesisHEK293 CellsHumansMAP Kinase Kinase 1MutationRNA SplicingDNA HelicasesMAP Kinase Kinase 1

Identifiers

PMID39388570
PMCPMC13492663

What OpenQuestion holds

Textmetadata
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.