Evidence map›Paper›PMID 34650270›Full record

ArticleNature biotechnology2022

Deletion and replacement of long genomic sequences using prime editing.

Tingting Jiang, Xiao-Ou Zhang, Zhiping Weng, Wen Xue

Open access · bronzeAbstract read
In one paragraph

Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed
11.2field-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

133 citing papers in PubMed, 183 citations in OpenAlex.

  1. Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Transposase-Assisted Donor Tethering Boosts Large-Fragment HDR in Plants.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. 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
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026
    Review
  19. Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  20. Review

73 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

4 authors at 2 institutions in 2 countries.

Tingting JiangRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Xiao-Ou ZhangProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-2027-1313
Zhiping WengProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Wen XueRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. wen.xue@umassmed.edu.ORCID http://orcid.org/0000-0002-9797-8042
University of Massachusetts Chan Medical School · USTongji University · CN

Funding

Vector Immunology CoreP01HL158506 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Dan Wang · 2021 to 2026
$19.5M
Viral Vector CoreP01HL131471 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FLOTTE, TERENCE R. · 2016 to 2020
$11.3M
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
Using base editing to investigate CFTR polymorphisms in lung diseasesK99HL153940 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI JIANG, TINGTING · 2021 to 2022
$234k
NHLBI NIH HHS DP2 HL137167NHLBI NIH HHS K99 HL153940NHLBI NIH HHS P01 HL131471NHLBI NIH HHS P01 HL158506NHLBI NIH HHS UG3 HL147367NHLBI NIH HHS UH3 HL147367
6 · The paper itself

Abstract

Genomic insertions, duplications and insertion/deletions (indels), which account for ~14% of human pathogenic mutations, cannot be accurately or efficiently corrected by current gene-editing methods, especially those that involve larger alterations (>100 base pairs (bp)). Here, we optimize prime editing (PE) tools for creating precise genomic deletions and direct the replacement of a genomic fragment ranging from ~1 kilobases (kb) to ~10 kb with a desired sequence (up to 60 bp) in the absence of an exogenous DNA template. By conjugating Cas9 nuclease to reverse transcriptase (PE-Cas9) and combining it with two PE guide RNAs (pegRNAs) targeting complementary DNA strands, we achieve precise and specific deletion and repair of target sequences via using this PE-Cas9-based deletion and repair (PEDAR) method. PEDAR outperformed other genome-editing methods in a reporter system and at endogenous loci, efficiently creating large and precise genomic alterations. In a mouse model of tyrosinemia, PEDAR removed a 1.38-kb pathogenic insertion within the Fah gene and precisely repaired the deletion junction to restore FAH expression in liver.

Indexed as

CRISPR-Cas SystemsGene EditingAnimalsEndonucleasesGenomeMiceRNA, Guide, CRISPR-Cas SystemsEndonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34650270
PMCPMC8847310
OpenAlexW3207691330

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.