Evidence map›Paper›PMID 40082411›Full record

ArticleNature communications2025

Integration of therapeutic cargo into the human genome with programmable type V-K CAST.

Jason Liu, Daniela S Aliaga Goltsman, Lisa M Alexander, Khak Khak Khayi, Jennifer H Hong, Drew T Dunham, Christine A Romano, Morayma M Temoche-Diaz, Shailaja Chadha, Rodrigo Fregoso Ocampo and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
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  13. Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Gene Therapy Techniques and Delivery Methods (Review).Sovremennye tekhnologii v meditsine · 2025
    Review
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

23 authors.

Jason Liu *Metagenomi, Inc, Emeryville, CA, 94608, United States of America.
Daniela S Aliaga Goltsman *Metagenomi, Inc, Emeryville, CA, 94608, United States of America.
Lisa M AlexanderMetagenomi, Inc, Emeryville, CA, 94608, United States of America.ORCID http://orcid.org/0000-0003-0152-4554
Khak Khak KhayiMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Jennifer H HongMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Drew T DunhamMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Christine A RomanoMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Morayma M Temoche-DiazMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Shailaja ChadhaMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Rodrigo Fregoso OcampoMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Jennifer Oki-O'ConnellMetagenomi, Inc, Emeryville, CA, 94608, United States of America.ORCID http://orcid.org/0000-0003-0147-0269
Owen P JansonMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Keirstinne TurciosMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Liliana Gonzalez-OsorioMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Jared MuyssonMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Jenat RahmanMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Sarah M LaperriereMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Audra E DevotoMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Cindy J CastelleMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Cristina N ButterfieldMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Gregory J CostMetagenomi, Inc, Emeryville, CA, 94608, United States of America.
Christopher T BrownMetagenomi, Inc, Emeryville, CA, 94608, United States of America. ctb@metagenomi.co.ORCID http://orcid.org/0000-0002-7758-6447
Brian C ThomasMetagenomi, Inc, Emeryville, CA, 94608, United States of America.

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

CRISPR-associated (Cas) transposases (CAST) are RNA-guided systems capable of programmable integration of large segments of DNA without creating double-strand breaks. Engineered Cascade CAST function in human cells but are challenging to deploy due to the complexity of the targeting components. Unlike Cascade, which require three Cas proteins, type V-K CAST require a single Cas12k effector for targeting. Here, we show that compact type V-K CAST from uncultivated microbes are repurposable for programmable DNA integration into the genome of human cells. Engineering for nuclear localization and function enables integration of a therapeutically relevant transgene at a safe-harbor site in multiple human cell types. Notably, off-targets are rare events reproducibly found in specific genomic regions. These CAST advancements are expected to accelerate applications of genome editing to therapeutic development, biotechnology, and synthetic biology.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsGene EditingGenome, HumanTransposasesDNAHEK293 CellsHumansRNA, Guide, CRISPR-Cas SystemsTransgenesCRISPR-Associated ProteinsDNARNA, Guide, CRISPR-Cas SystemsTransposases

Identifiers

PMID40082411
PMCPMC11906591

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.