Evidence map›Paper›PMID 23992846›Full record

ArticleCell2013

Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity.

F Ann Ran, Patrick D Hsu, Chie-Yu Lin, Jonathan S Gootenberg, Silvana Konermann, Alexandro E Trevino, David A Scott, Azusa Inoue, Shogo Matoba, Yi Zhang and 1 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1,842 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,842citing papers in PubMed, 1 pooled it
140.5field-weighted citation impact, top 1% 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

1,842 citing papers in PubMed, 1 synthesis or guideline pooled it, 3,348 citations in OpenAlex.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Advances in Therapies for Mucopolysaccharidoses.Current issues in molecular biology · 2026
    Review
  16. Article
  17. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  18. Review
  19. Article
  20. Article

1,782 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

F Ann RanBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Patrick D Hsu
Chie-Yu Lin
Jonathan S Gootenberg
Silvana Konermann
Alexandro E Trevino
David A Scott
Azusa Inoue
Shogo Matoba
Yi Zhang
Feng Zhang
Broad Institute · USHoward Hughes Medical Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease MutationsR01DK097768 · NIDDK · BROAD INSTITUTE, INC. · PI COWAN, CHAD ALBERT, ZHANG, FENG · 2012 to 2016
$11.0M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
Epigenetic and chemical approaches to generate function beta cellsU01DK089565 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YI · 2010 to 2014
$3.0M
Mechanisms of Polycomb SilencingR01GM068804 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZHANG, YI · 2003 to 2010
$2.1M
Howard Hughes Medical InstituteNCCDPHP CDC HHS 1DP1-MH100706NIDDK NIH HHS 1R01-DK097768NIDDK NIH HHS R01 DK097768NIDDK NIH HHS U01DK089565NIGMS NIH HHS GM68804NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753NIMH NIH HHS DP1 MH100706
6 · The paper itself

Abstract

Targeted genome editing technologies have enabled a broad range of research and medical applications. The Cas9 nuclease from the microbial CRISPR-Cas system is targeted to specific genomic loci by a 20 nt guide sequence, which can tolerate certain mismatches to the DNA target and thereby promote undesired off-target mutagenesis. Here, we describe an approach that combines a Cas9 nickase mutant with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity, simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and extends the number of specifically recognized bases for target cleavage. We demonstrate that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency. This versatile strategy enables a wide variety of genome editing applications that require high specificity.

Indexed as

DNA Breaks, Double-StrandedGenomeAnimalsBase SequenceGene TargetingMiceMolecular Sequence DataRNA, Small UntranslatedStreptococcus pyogenesZygoteRNA, Small Untranslated

Identifiers

PMID23992846
PMCPMC3856256
OpenAlexW2167380395

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.