Evidence map›Paper›PMID 33837189›Full record

ArticleNature communications2021

Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice.

Pengpeng Liu, Shun-Qing Liang, Chunwei Zheng, Esther Mintzer, Yan G Zhao, Karthikeyan Ponnienselvan, Aamir Mir, Erik J Sontheimer, Guangping Gao, Terence R Flotte and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 1 pooled it
18.3field-weighted citation impact, top 1% 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

195 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.

  1. Pooled it
  2. Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

135 more citing papers are in PubMed but not listed here.

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

12 authors at 1 institution in 1 country.

Pengpeng Liu *Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Shun-Qing Liang *RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Chunwei ZhengRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Esther MintzerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Yan G ZhaoDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Karthikeyan PonnienselvanDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Aamir MirRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.ORCID 0000-0003-0144-3914
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.ORCID 0000-0002-0881-0310
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.ORCID 0000-0003-0097-9012
Terence R FlotteHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.ORCID 0000-0002-8255-0588
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA. scot.wolfe@umassmed.edu.ORCID 0000-0002-7042-201X
Wen XueRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. wen.xue@umassmed.edu.ORCID 0000-0002-9797-8042
University of Massachusetts Chan Medical School · US

Funding

Viral Vector CoreP01HL131471 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI XUE, WEN · 2016 to 2020
$11.3M
Next-generation antisense therapeutics for ALS and frontotemporal dementiaR01NS111990 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Robert H Brown, Jonathan K Watts · 2019 to 2026
$5.2M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUH3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2021 to 2022
$3.1M
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 TR002668NCATS NIH HHS UH3 TR002668NHLBI NIH HHS DP2 HL137167NHLBI NIH HHS P01 HL131471NHLBI NIH HHS UG3 HL147367NIGMS NIH HHS R01 GM115911NINDS NIH HHS R01 NS111990
6 · The paper itself

Abstract

Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Here we report an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency in both fluorescent reporter cells and at endogenous loci in cultured cell lines. Using this genome modification system, we could also seed tumor formation through somatic cell editing in the adult mouse. Finally, we successfully utilize dual adeno-associated virus (AAVs) for the delivery of a split-intein prime editor and demonstrate that this system enables the correction of a pathogenic mutation in the mouse liver. Our findings further establish the broad potential of this genome editing technology for the directed installation of sequence modifications in vivo, with important implications for disease modeling and correction.

Indexed as

AllelesAnimalsCarcinogenesisCRISPR-Cas SystemsDependovirusDisease Models, AnimalGene EditingHEK293 CellsHeLa CellsHumansMiceNeoplasmsTransfection

Identifiers

PMID33837189
PMCPMC8035190
OpenAlexW3145074783

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.