Evidence map›Paper›PMID 36217031›Full record

ArticleNature biotechnology2023

Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome.

Matthew G Durrant, Alison Fanton, Josh Tycko, Michaela Hinks, Sita S Chandrasekaran, Nicholas T Perry, Julia Schaepe, Peter P Du, Peter Lotfy, Michael C Bassik and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed
15.8field-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

128 citing papers in PubMed, 194 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Editor's pick: Stylus Medicine.Nature biotechnology · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. 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
  17. Cp36 serine recombinase as a new tool for zebrafish transgenesis.bioRxiv : the preprint server for biology · 2026
    Article
  18. Article
  19. Article
  20. Multi-Targeting Non-Specific Genome Engineering in Bacteria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Matthew G Durrant *Arc Institute, Palo Alto, CA, USA.
Alison Fanton *Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Josh Tycko *Department of Genetics, Stanford University, Stanford, CA, USA.
Michaela HinksDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Sita S ChandrasekaranDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Nicholas T PerryDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Julia SchaepeDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Peter P DuDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2652-0541
Peter LotfyLaboratory of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0809-7073
Michael C BassikDepartment of Genetics, Stanford University, Stanford, CA, USA. bassik@stanford.edu.ORCID http://orcid.org/0000-0001-5185-8427
Lacramioara BintuDepartment of Bioengineering, Stanford University, Stanford, CA, USA. lbintu@stanford.edu.ORCID http://orcid.org/0000-0001-5443-6633
Ami S BhattDepartment of Genetics, Stanford University, Stanford, CA, USA. asbhatt@stanford.edu.ORCID http://orcid.org/0000-0001-8099-2975
Patrick D HsuArc Institute, Palo Alto, CA, USA. pdhsu@berkeley.edu.ORCID http://orcid.org/0000-0002-9380-2648
Stanford University · USUniversity of California, Berkeley · USSalk Institute for Biological Studies · USPalo Alto Institute · USStanford Medicine · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Single-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulationR35GM128947 · NIGMS · STANFORD UNIVERSITY · PI Lacramioara Bintu · 2018 to 2026
$3.1M
Culture-free pathogen tracking in hospitalized patientsR01AI143757 · NIAID · STANFORD UNIVERSITY · PI BHATT, AMI SIDDHARTH · 2020 to 2023
$3.0M
Eukaryotic transcriptome engineering via sequence-specific regulation of endogenous RNADP5OD021369 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI HSU, PATRICK · 2015 to 2018
$2.4M
Biology and Biotechnology of Cell and Gene TherapyT32GM139780 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Amy Elizabeth Herr, Dirk Hockemeyer · 2021 to 2026
$2.4M
Emerging novel mechanisms of antibiotic resistance in the prevalent foodborne pathogen, SalmonellaR01AI148623 · NIAID · STANFORD UNIVERSITY · PI BHATT, AMI SIDDHARTH · 2019 to 2023
$2.0M
Molecular tools for targeting RNAR01GM131073 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HSU, PATRICK · 2019 to 2022
$1.3M
High-throughput dissection of transcriptional regulation in kidney diseaseK00DK126120 · NIDDK · HARVARD MEDICAL SCHOOL · PI TYCKO, JOSH · 2022 to 2025
$355k
High-throughput dissection of transcriptional regulation in kidney diseaseF99DK126120 · NIDDK · STANFORD UNIVERSITY · PI TYCKO, JOSH · 2020 to 2021
$78k
NCI NIH HHS T32 CA009302NHGRI NIH HHS UM1 HG009436NIAID NIH HHS R01 AI143757NIAID NIH HHS R01 AI148623NIDDK NIH HHS F99 DK126120NIDDK NIH HHS K00 DK126120NIGMS NIH HHS R01 GM131073NIGMS NIH HHS R35 GM128947NIGMS NIH HHS T32 GM139780NIH HHS DP5 OD021369
6 · The paper itself

Abstract

Large serine recombinases (LSRs) are DNA integrases that facilitate the site-specific integration of mobile genetic elements into bacterial genomes. Only a few LSRs, such as Bxb1 and PhiC31, have been characterized to date, with limited efficiency as tools for DNA integration in human cells. In this study, we developed a computational approach to identify thousands of LSRs and their DNA attachment sites, expanding known LSR diversity by >100-fold and enabling the prediction of their insertion site specificities. We tested their recombination activity in human cells, classifying them as landing pad, genome-targeting or multi-targeting LSRs. Overall, we achieved up to seven-fold higher recombination than Bxb1 and genome integration efficiencies of 40-75% with cargo sizes over 7 kb. We also demonstrate virus-free, direct integration of plasmid or amplicon libraries for improved functional genomics applications. This systematic discovery of recombinases directly from microbial sequencing data provides a resource of over 60 LSRs experimentally characterized in human cells for large-payload genome insertion without exposed DNA double-stranded breaks.

Indexed as

Genetic EngineeringIntegrasesGenome, HumanGenomic LibraryHumansTransfectionIntegrases

Identifiers

PMID36217031
PMCPMC10083194
OpenAlexW4304080659

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.