Evidence map›Paper›PMID 37291100›Full record

ArticleNature communications2023

Template-jumping prime editing enables large insertion and exon rewriting in vivo.

Chunwei Zheng, Bin Liu, Xiaolong Dong, Nicholas Gaston, Erik J Sontheimer, Wen Xue

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
8.8field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026
    Review
  12. Article
  13. Review
  14. Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  15. Review
  16. Review
  17. Advancements in CRISPR-basedFrontiers in genome editing · 2026
    Review
  18. Review
  19. The Template-Jumping Editing Approach inInternational journal of molecular sciences · 2025
    Article
  20. 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

6 authors at 1 institution in 1 country.

Chunwei Zheng *RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-2084-5567
Bin Liu *RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-3168-8456
Xiaolong DongRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Nicholas GastonRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID 0000-0002-3862-9002
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. erik.sontheimer@umassmed.edu.ORCID 0000-0002-0881-0310
Wen XueRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. wen.xue@umassmed.edu.ORCID 0000-0002-9797-8042
University of Massachusetts Chan Medical School · US

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
Develop combinatorial non-viral and viral CRISPR delivery for lung diseasesUG3HL147367 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANDERSON, DANIEL G, GAO, GUANGPING · 2018 to 2020
$2.7M
CRISPR-based modular therapy for precision medicineDP2HL137167 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI XUE, WEN · 2016 to 2016
$2.5M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUG3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2018 to 2020
$2.5M
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
NCATS NIH HHS UG3 TR002668NHLBI NIH HHS DP2 HL137167NHLBI NIH HHS P01 HL158506NHLBI NIH HHS UG3 HL147367NHLBI NIH HHS UH3 HL147367NIGMS NIH HHS R01 GM115911
6 · The paper itself

Abstract

Targeted insertion of large DNA fragments holds promise for genome engineering and gene therapy. Prime editing (PE) effectively inserts short (<50 bp) sequences. Employing paired prime editing guide RNAs (pegRNAs) has enabled PE to better mediate relatively large insertions in vitro, but the efficiency of larger insertions (>400 bp) remains low and in vivo application has not been demonstrated. Inspired by the efficient genomic insertion mechanism of retrotransposons, we develop a template-jumping (TJ) PE approach for the insertion of large DNA fragments using a single pegRNA. TJ-pegRNA harbors the insertion sequence as well as two primer binding sites (PBSs), with one PBS matching a nicking sgRNA site. TJ-PE precisely inserts 200 bp and 500 bp fragments with up to 50.5 and 11.4% efficiency, respectively, and enables GFP (~800 bp) insertion and expression in cells. We transcribe split circular TJ-petRNA in vitro via a permuted group I catalytic intron for non-viral delivery in cells. Finally, we demonstrate that TJ-PE can rewrite an exon in the liver of tyrosinemia I mice to reverse the disease phenotype. TJ-PE has the potential to insert large DNA fragments without double-stranded DNA breaks and facilitate mutation hotspot exon rewriting in vivo.

Indexed as

DNAGene EditingAnimalsCRISPR-Cas SystemsDNA Breaks, Double-StrandedExonsGenomeMiceDNA

Identifiers

PMID37291100
PMCPMC10250319
OpenAlexW4379929812

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.