Evidence map›Paper›PMID 36522342›Full record

ArticleNature communications2022

Compact Cas9d and HEARO enzymes for genome editing discovered from uncultivated microbes.

Daniela S Aliaga Goltsman, Lisa M Alexander, Jyun-Liang Lin, Rodrigo Fregoso Ocampo, Benjamin Freeman, Rebecca C Lamothe, Andres Perez Rivas, Morayma M Temoche-Diaz, Shailaja Chadha, Natalie Nordenfelt and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026
    Article
  7. Article
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  9. Review
  10. Article
  11. Article
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  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Genome editing with natural and engineered CjCas9 orthologs.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  20. Article
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

17 authors at 2 institutions in 2 countries.

Daniela S Aliaga GoltsmanMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA. daniela@metagenomi.co.
Lisa M AlexanderMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.ORCID 0000-0003-0152-4554
Jyun-Liang LinMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Rodrigo Fregoso OcampoMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Benjamin FreemanMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Rebecca C LamotheMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Andres Perez RivasMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Morayma M Temoche-DiazMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Shailaja ChadhaMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Natalie NordenfeltMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.ORCID 0000-0002-3484-029X
Owen P JansonMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Ian BarrMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Audra E DevotoMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Gregory J CostMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Cristina N ButterfieldMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Brian C ThomasMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA.
Christopher T BrownMetagenomi Inc. 1545 Park Ave, Emeryville, CA, 94608, USA. ctb@metagenomi.co.ORCID 0000-0002-7758-6447
Milagen (United States) · USInstitute of Metagenomics and Microbial Technologies (Slovenia) · SI

Funding

Pacific Biosciences PacBio RS Single Molecule Real Time SequencerS10OD018174 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROKHSAR, DANIEL SOLEYMAN · 2014 to 2014
$600k
NIH HHS S10 OD018174
6 · The paper itself

Abstract

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. However, to further expand the therapeutic application of these tools there is a need for targetable systems that are small enough to be delivered efficiently. Here, we mined an extensive genome-resolved metagenomics database and identified families of uncharacterized RNA-guided, compact nucleases (between 450 and 1,050 aa). We report that Cas9d, a new CRISPR type II subtype, contains Zinc-finger motifs and high arginine content, features that we also found in nucleases related to HEARO effectors. These enzymes exhibit diverse biochemical characteristics and are broadly targetable. We show that natural Cas9d enzymes are capable of genome editing in mammalian cells with >90% efficiency, and further engineered nickase variants into the smallest base editors active in E. coli and human cells. Their small size, broad targeting potential, and translatability suggest that Cas9d and HEARO systems will enable a variety of genome editing applications.

Indexed as

Escherichia coliGene EditingAnimalsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEndonucleasesHumansMammalsRibonucleasesRNAEndonucleasesRibonucleasesRNA

Identifiers

PMID36522342
PMCPMC9755519
OpenAlexW4311760607

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.