Evidence map›Paper›PMID 36459645›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Decorating chromatin for enhanced genome editing using CRISPR-Cas9.

Evelyn Chen, Enrique Lin-Shiao, Marena Trinidad, Mohammad Saffari Doost, David Colognori, Jennifer A Doudna

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
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

30 citing papers in PubMed, 48 citations in OpenAlex.

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  20. CRISPR/Cas9 as a Mutagenic Factor.International journal of molecular sciences · 2024
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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

6 authors at 2 institutions in 1 country.

Evelyn ChenDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.ORCID 0000-0003-1102-6997
Enrique Lin-ShiaoDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.ORCID 0000-0001-5396-9614
Marena TrinidadDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Mohammad Saffari DoostDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.ORCID 0000-0001-9236-3957
David ColognoriDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720.ORCID 0000-0001-9161-999X
University of California, San Francisco · USLawrence Berkeley National Laboratory · US

Funding

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
Decorating chromatin for precise genome editing using CRISPR CasF32GM142146 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI LIN SHIAO, ENRIQUE · 2021 to 2021
$20k
NHGRI NIH HHS RM1 HG009490NIGMS NIH HHS F32 GM142146
6 · The paper itself

Abstract

CRISPR-associated (Cas) enzymes have revolutionized biology by enabling RNA-guided genome editing. Homology-directed repair (HDR) in the presence of donor templates is currently the most versatile method to introduce precise edits following CRISPR-Cas-induced double-stranded DNA cuts, but HDR efficiency is generally low relative to end-joining pathways that lead to insertions and deletions (indels). We tested the hypothesis that HDR could be increased using a Cas9 construct fused to PRDM9, a chromatin remodeling factor that deposits histone methylations H3K36me3 and H3K4me3 to mediate homologous recombination in human cells. Our results show that the fusion protein contacts chromatin specifically at the Cas9 cut site in the genome to increase the observed HDR efficiency by threefold and HDR:indel ratio by fivefold compared with that induced by unmodified Cas9. HDR enhancement occurred in multiple cell lines with no increase in off-target genome editing. These findings underscore the importance of chromatin features for the balance between DNA repair mechanisms during CRISPR-Cas genome editing and provide a strategy to increase HDR efficiency.

Indexed as

ChromatinCRISPR-Cas SystemsGene EditingHistone-Lysine N-MethyltransferaseHomologous RecombinationHumansRecombinational DNA RepairChromatinHistone-Lysine N-MethyltransferasePRDM9 protein, humanchromatinCRISPRepigeneticsgenome editing

Identifiers

PMID36459645
PMCPMC9894255
OpenAlexW4310772609

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.