Evidence map›Paper›PMID 30670702›Full record

ArticleNature communications2019

Engineering of CRISPR-Cas12b for human genome editing.

Jonathan Strecker, Sara Jones, Balwina Koopal, Jonathan Schmid-Burgk, Bernd Zetsche, Linyi Gao, Kira S Makarova, Eugene V Koonin, Feng Zhang

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
–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

182 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Simultaneous molecular detection ofFrontiers in cellular and infection microbiology · 2026
    Article
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  18. From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  19. An Engineered PfAgo with Wide Catalytic Temperature Range and Substrate Spectrum.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  20. Article

122 more citing papers are in PubMed but not listed here.

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.

Jonathan StreckerHoward Hughes Medical Institute, Cambridge, USA.
Sara JonesHoward Hughes Medical Institute, Cambridge, USA.
Balwina KoopalHoward Hughes Medical Institute, Cambridge, USA.ORCID http://orcid.org/0000-0002-5310-7528
Jonathan Schmid-BurgkHoward Hughes Medical Institute, Cambridge, USA.
Bernd ZetscheHoward Hughes Medical Institute, Cambridge, USA.
Linyi GaoHoward Hughes Medical Institute, Cambridge, USA.ORCID http://orcid.org/0000-0002-3579-0327
Kira S MakarovaNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.ORCID http://orcid.org/0000-0003-3943-8299
Feng ZhangHoward Hughes Medical Institute, Cambridge, USA. zhang@broadinstitute.org.

Funding

Programmable RNA-targeting toolsR01HG009761 · NHGRI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2024
$7.5M
Exploration of Diverse Mobile Genetic Elements for Precision Genome ManipulationDP1HL141201 · NHLBI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2021
$6.2M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
NHGRI NIH HHS R01 HG009761NHLBI NIH HHS DP1 HL141201NIMH NIH HHS R01 MH110049
6 · The paper itself

Abstract

The type-V CRISPR effector Cas12b (formerly known as C2c1) has been challenging to develop for genome editing in human cells, at least in part due to the high temperature requirement of the characterized family members. Here we explore the diversity of the Cas12b family and identify a promising candidate for human gene editing from Bacillus hisashii, BhCas12b. However, at 37 °C, wild-type BhCas12b preferentially nicks the non-target DNA strand instead of forming a double strand break, leading to lower editing efficiency. Using a combination of approaches, we identify gain-of-function mutations for BhCas12b that overcome this limitation. Mutant BhCas12b facilitates robust genome editing in human cell lines and ex vivo in primary human T cells, and exhibits greater specificity compared to S. pyogenes Cas9. This work establishes a third RNA-guided nuclease platform, in addition to Cas9 and Cpf1/Cas12a, for genome editing in human cells.

Indexed as

CRISPR-Cas SystemsGene EditingGenome, HumanBacillusBacterial ProteinsCell LineDeoxyribonucleasesHumansModels, MolecularMutationProtein ConformationT-LymphocytesBacterial ProteinsDeoxyribonucleases

Identifiers

PMID30670702
PMCPMC6342934

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.