Evidence map›Paper›PMID 34043941›Full record

ArticleCell2021

Efficient embryonic homozygous gene conversion via RAD51-enhanced interhomolog repair.

Jonathan J Wilde, Tomomi Aida, Ricardo C H Del Rosario, Tobias Kaiser, Peimin Qi, Martin Wienisch, Qiangge Zhang, Steven Colvin, Guoping Feng

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

46 citing papers in PubMed, 83 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Jonathan J WildeDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Electronic address: wildej@mit.edu.
Tomomi AidaDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Ricardo C H Del RosarioStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tobias KaiserDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Peimin QiDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Martin WienischDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Qiangge ZhangDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Steven ColvinDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Guoping FengDepartment of Brain & Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: fengg@mit.edu.
McGovern Institute for Brain Research · USBroad Institute · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Res Support CoreP50MH094271 · NIMH · HARVARD UNIVERSITY · PI HENSCH, TAKAO K · 2011 to 2022
$18.6M
Knockin marmoset reporters for non-invasive measuring of genome-editing efficiencyU24OD026638 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FENG, GUOPING · 2018 to 2022
$4.0M
NIGMS NIH HHS T32 GM007287NIH HHS U24 OD026638NIMH NIH HHS P50 MH094271
6 · The paper itself

Abstract

Searching for factors to improve knockin efficiency for therapeutic applications, biotechnology, and generation of non-human primate models of disease, we found that the strand exchange protein RAD51 can significantly increase Cas9-mediated homozygous knockin in mouse embryos through an interhomolog repair (IHR) mechanism. IHR is a hallmark of meiosis but only occurs at low frequencies in somatic cells, and its occurrence in zygotes is controversial. Using multiple approaches, we provide evidence for an endogenous IHR mechanism in the early embryo that can be enhanced by RAD51. This process can be harnessed to generate homozygotes from wild-type zygotes using exogenous donors and to convert heterozygous alleles into homozygous alleles without exogenous templates. Furthermore, we identify additional IHR-promoting factors and describe features of IHR events. Together, our findings show conclusive evidence for IHR in mouse embryos and describe an efficient method for enhanced gene conversion.

Indexed as

Gene ConversionAllelesAnimalsBase SequenceCalcium-Binding ProteinsCell Cycle ProteinsChromosomes, MammalianCRISPR-Associated Protein 9DNA Breaks, Double-StrandedDNA RepairEmbryo, MammalianFemaleGenetic LociHomologous RecombinationHomozygoteHumansBCCIP protein, humanCalcium-Binding ProteinsCell Cycle ProteinsCRISPR-Associated Protein 9Nuclear ProteinsRad51 RecombinaseRibonucleoproteinsBCCIPCRISPRDNA repairgene conversiongenome editinghomologous recombinationinterhomolog repairRAD51USP1WDR48

Identifiers

PMID34043941
PMCPMC8240950
OpenAlexW3164768127

What OpenQuestion holds

Textmetadata
LicenceTDM
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.