Evidence map›Paper›PMID 34887556›Full record

ArticleNature biotechnology2022

Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing.

Andrew V Anzalone, Xin D Gao, Christopher J Podracky, Andrew T Nelson, Luke W Koblan, Aditya Raguram, Jonathan M Levy, Jaron A M Mercer, David R Liu

Open access · greenAbstract 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 380 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
380citing papers in PubMed, 1 pooled it
29.5field-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

380 citing papers in PubMed, 1 synthesis or guideline pooled it, 543 citations in OpenAlex.

  1. Pooled it
  2. Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027
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320 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

9 authors at 1 institution in 1 country.

Andrew V Anzalone *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Xin D Gao *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2917-2060
Christopher J Podracky *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Andrew T NelsonMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Luke W KoblanMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Aditya RaguramMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jonathan M LevyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8061-7953
Jaron A M MercerMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0003-0346-5033
Broad Institute · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
PedGeneRx - Admin Supplement to Base Editing and Prime Editing for Sickle Cell Disease R01R01HL156647 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Agnieszka Czechowicz, DAVID R LIU · 2021 to 2026
$4.8M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R01 HL156647NIAID NIH HHS U01 AI142756NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

The targeted deletion, replacement, integration or inversion of genomic sequences could be used to study or treat human genetic diseases, but existing methods typically require double-strand DNA breaks (DSBs) that lead to undesired consequences, including uncontrolled indel mixtures and chromosomal abnormalities. Here we describe twin prime editing (twinPE), a DSB-independent method that uses a prime editor protein and two prime editing guide RNAs (pegRNAs) for the programmable replacement or excision of DNA sequences at endogenous human genomic sites. The two pegRNAs template the synthesis of complementary DNA flaps on opposing strands of genomic DNA, which replace the endogenous DNA sequence between the prime-editor-induced nick sites. When combined with a site-specific serine recombinase, twinPE enabled targeted integration of gene-sized DNA plasmids (>5,000 bp) and targeted sequence inversions of 40 kb in human cells. TwinPE expands the capabilities of precision gene editing and might synergize with other tools for the correction or complementation of large or complex human pathogenic alleles.

Indexed as

CRISPR-Cas SystemsGene EditingBase SequenceChromosome InversionDNAHumansRNA, Guide, CRISPR-Cas SystemsDNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34887556
PMCPMC9117393
OpenAlexW4200345742

What OpenQuestion 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 OpenQuestion graph.