Evidence map›Paper›PMID 41372199›Full record

ArticleNature communications2025

Ligase-mediated programmable genomic integration (L-PGI).

Angela X Nan, Michael Chickering, Christopher L Bartolome, Neeta Shadija, Dan Li, Brett J G Estes, Jessica Von Stetina, Wei Li, Jason Andresen, Kaivalya Molugu and 14 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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

24 authors.

Angela X Nan *Tome Biosciences Inc, Watertown, MA, USA.
Michael Chickering *Replace Therapeutics, LLC, a direct and wholly owned subsidiary of Tome Biosciences Inc, Berkeley, CA, USA.
Christopher L BartolomeTome Biosciences Inc, Watertown, MA, USA.
Neeta ShadijaTome Biosciences Inc, Watertown, MA, USA.
Dan LiTome Biosciences Inc, Watertown, MA, USA.
Brett J G EstesTome Biosciences Inc, Watertown, MA, USA.
Jessica Von StetinaTome Biosciences Inc, Watertown, MA, USA.
Wei LiTome Biosciences Inc, Watertown, MA, USA.
Jason AndresenTome Biosciences Inc, Watertown, MA, USA.
Kaivalya MoluguTome Biosciences Inc, Watertown, MA, USA.
Ravindra AmunugamaTome Biosciences Inc, Watertown, MA, USA.
Minggang FangTome Biosciences Inc, Watertown, MA, USA.
Chen BaiTome Biosciences Inc, Watertown, MA, USA.
Jie WangTome Biosciences Inc, Watertown, MA, USA.
Davood NorouziTome Biosciences Inc, Watertown, MA, USA.
Jesse C CochraneTome Biosciences Inc, Watertown, MA, USA.
Jason T GatlinTome Biosciences Inc, Watertown, MA, USA.
Maike Thamsen DunyakTome Biosciences Inc, Watertown, MA, USA.
Sandeep KumarTome Biosciences Inc, Watertown, MA, USA.
Leonard ChavezReplace Therapeutics, LLC, a direct and wholly owned subsidiary of Tome Biosciences Inc, Berkeley, CA, USA.
Anmol SethReplace Therapeutics, LLC, a direct and wholly owned subsidiary of Tome Biosciences Inc, Berkeley, CA, USA.
Shakked HalperinReplace Therapeutics, LLC, a direct and wholly owned subsidiary of Tome Biosciences Inc, Berkeley, CA, USA. shakkedhalperin@gmail.com.ORCID http://orcid.org/0000-0002-4221-3595
Jonathan D FinnTome Biosciences Inc, Watertown, MA, USA. jdfinn@outlook.com.ORCID http://orcid.org/0009-0002-3707-7872
Jenny XieTome Biosciences Inc, Watertown, MA, USA. jx46@netzero.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since their discovery, CRISPR systems have been repurposed for programmable targeted genomic editing, leading to applications for gene disruption, single base editing, insertion, deletion, and manipulation of short genomic sequences. Pairing Cas9 nickase with reverse transcriptase allows applications for insertion, substitution, and deletion of short genomic sequences from an RNA template without generating double stranded breaks however this technology typically shows reduced efficacy in post mitotic cells, limiting its translatability in vivo. Here we present a novel, ligase-based method that addresses these limiations. We introduce edits through delivery and ligation of a synthetic DNA donor to genomic nicks created with Cas9 nickase and report editing activity in cell lines, primary cell cultures, and adult mice via nonviral delivery. With favorable on target outcomes compared to transcription-based editing in key cell types, good tolerability, and deliverability, ligation-mediated gene editing has the potential to further advance genomic medicine.

Indexed as

CRISPR-Cas SystemsGene EditingLigasesAnimalsGenomicsHEK293 CellsHumansMiceLigases

Identifiers

PMID41372199
PMCPMC12808795

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.