Evidence map›Paper›PMID 30518407›Full record

ArticleGenome biology2018

NmeCas9 is an intrinsically high-fidelity genome-editing platform.

Nadia Amrani, Xin D Gao, Pengpeng Liu, Alireza Edraki, Aamir Mir, Raed Ibraheim, Ankit Gupta, Kanae E Sasaki, Tong Wu, Paul D Donohoue and 9 more

Abstract readComparative StudyEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing 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

82 citing papers in PubMed.

  1. Review
  2. Wheat's Up with CRISPR-Cas-Current Advances, Obstacles and Perspectives.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Mechanism of Cas9 inhibition by AcrIIA11.Nucleic acids research · 2025
    Article
  17. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  18. Article
  19. Article
  20. AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article

22 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

19 authors.

Nadia AmraniRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Xin D GaoRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Pengpeng LiuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Alireza EdrakiRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Aamir MirRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Raed IbraheimRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Ankit GuptaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Kanae E SasakiRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Tong WuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Paul D DonohoueCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Alexander H SettleCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Alexandra M LiedCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Kyle McGovernCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Chris K FullerCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Peter CameronCaribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA, 94710, USA.
Thomas G FazzioProgram in Molecular Medicine, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Lihua Julie ZhuProgram in Molecular Medicine, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA. erik.sontheimer@umassmed.edu.ORCID 0000-0002-0881-0310

Funding

Engineered Cas9 Nucleases with Single-Genomic-Site Precision for CYBB CorrectionR01GM115911 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SONTHEIMER, ERIK J., WOLFE, SCOT A · 2016 to 2019
$1.6M
NIGMS NIH HHS R01 GM115911NIH HHS GM115911
6 · The paper itself

Abstract

backgroundThe development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wildtype SpyCas9 can induce significant levels of unintended mutations at near-cognate sites, necessitating substantial efforts toward the development of strategies to minimize off-target activity. Although the genome-editing potential of thousands of other Cas9 orthologs remains largely untapped, it is not known how many will require similarly extensive engineering to achieve single-site accuracy within large genomes. In addition to its off-targeting propensity, SpyCas9 is encoded by a relatively large open reading frame, limiting its utility in applications that require size-restricted delivery strategies such as adeno-associated virus vectors. In contrast, some genome-editing-validated Cas9 orthologs are considerably smaller and therefore better suited for viral delivery.

resultsHere we show that wildtype NmeCas9, when programmed with guide sequences of the natural length of 24 nucleotides, exhibits a nearly complete absence of unintended editing in human cells, even when targeting sites that are prone to off-target activity with wildtype SpyCas9. We also validate at least six variant protospacer adjacent motifs (PAMs), in addition to the preferred consensus PAM (5'-N

conclusionsOur results show that NmeCas9 is a naturally high-fidelity genome-editing enzyme and suggest that additional Cas9 orthologs may prove to exhibit similarly high accuracy, even without extensive engineering.

Indexed as

AnimalsCRISPR-Associated Protein 9Gene EditingHumansNeisseria meningitidisCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9Cas9CRISPRNeisseria meningitidisOff-targetProtospacer adjacent motifsgRNA

Identifiers

PMID30518407
PMCPMC6282386

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.