Evidence map›Paper›PMID 39962280›Full record

ArticleNature biotechnology2026

The reverse transcriptase domain of prime editors contributes to DNA repair in mammalian cells.

Chunwei Zheng, Gangming Zhang, Lilia J Dean, Erik J Sontheimer, Wen Xue

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Advances in CRISPR/Cas9-Based Gene Editing in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 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

5 authors.

Chunwei Zheng *RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-2084-5567
Gangming Zhang *RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-8488-2607
Lilia J DeanRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0001-2225-6395
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-0881-0310
Wen XueRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA. wen.xue@umassmed.edu.ORCID http://orcid.org/0000-0002-9797-8042

Funding

Vector Immunology CoreP01HL158506 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Terence R. Flotte · 2021 to 2026
$19.5M
Develop combinatorial non-viral and viral CRISPR delivery for lung diseasesUH3HL147367 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANDERSON, DANIEL G, GAO, GUANGPING · 2021 to 2022
$2.9M
In vivo prime editing for precision cancer mouse modelsR01CA275945 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Wen Xue · 2023 to 2026
$2.5M
Advanced Delivery Platforms for Base Editing In VivoR01GM150273 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ERIK J. SONTHEIMER, Wen Xue · 2023 to 2026
$2.4M
BD FACSAriaTM Fusion Fluoresence-Activated Cell SorterS10OD028576 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHRADER, CAROL E · 2020 to 2020
$565k
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) P01HL158506Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01GM150279Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) UH3HL147367NCI NIH HHS R01 CA275945NHLBI NIH HHS P01 HL158506NHLBI NIH HHS UH3 HL147367NIGMS NIH HHS R01 GM150273NIH HHS S10 OD028576
6 · The paper itself

Abstract

Reverse transcriptase (RT) has been shown to play a role in double-strand break repair in bacteria, yet the impact of the RT component of prime editors (PEs) on normal mammalian cellular functions is unclear. Here we show that overexpressed RT or PE increases short insertions and diminishes homology-directed repair following Cas9 cleavage at multiple loci in multiple cell lines. Live-cell imaging shows that RT and PEs are rapidly recruited to laser-induced DNA damage sites and promote endogenous repair, independent of known DNA damage sensors. Interestingly, RT-mCherry partially impairs green fluorescent protein-PARP1 recruitment. A compact PE without an RNase H domain shows reduced DNA repair activity and may therefore be more suitable for clinical application. These data reveal a role for untethered RT or the RT domain of PEs in the repair of chromosomal breaks, calling for evaluation of the long-term effect of PEs and retroviral RT in mammalian cells.

Indexed as

DNA RepairGene EditingRNA-Directed DNA PolymeraseAnimalsCell LineCRISPR-Cas SystemsDNA Breaks, Double-StrandedDNA DamageHEK293 CellsHumansProtein DomainsRNA-Directed DNA Polymerase

Identifiers

PMID39962280
PMCPMC13394396

What OpenQuestion holds

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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.