Evidence map›Paper›PMID 39039307›Full record

ArticleNature biotechnology2025

Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases.

Joana Ferreira da Silva, Connor J Tou, Emily M King, Madeline L Eller, David Rufino-Ramos, Linyuan Ma, Christopher R Cromwell, Jasna Metovic, Friederike M C Benning, Luke H Chao and 2 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
–field-weighted citation impact
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

51 citing papers in PubMed.

  1. Article
  2. Article
  3. Wheat's Up with CRISPR-Cas-Current Advances, Obstacles and Perspectives.International journal of molecular sciences · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. CRISPR-based functional genomics tools in vertebrate models.Experimental & molecular medicine · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Joana Ferreira da Silva *Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Connor J Tou *Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2444-4215
Emily M KingCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3489-3682
Madeline L EllerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
David Rufino-RamosCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5125-9667
Linyuan MaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Christopher R CromwellCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Jasna MetovicCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9146-1747
Friederike M C BenningDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1002-4204
Luke H ChaoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4849-4148
Florian S EichlerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. bkleinstiver@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-5469-0655

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Matthias Nahrendorf · 2019 to 2026
$19.5M
Validation of the GMFC-MLDU54NS115052 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Adeline Lucie Vanderver · 2019 to 2026
$14.3M
Comprehensive characterization of variants underlying heart and blood diseases with CRISPR base editingUM1HG012010 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel Evan Bauer, Luca Pinello · 2021 to 2026
$10.4M
Probing structural and biophysical mechanisms of mitochondrial membrane ultrastructureR35GM142553 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI Luke H. Chao · 2021 to 2026
$2.6M
Multiscale exploration of the functional non-coding genomeR35HG010717 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI PINELLO, LUCA · 2019 to 2023
$2.6M
Scalable Development of Custom Genome Editing TechnologiesDP2CA281401 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2022 to 2025
$2.5M
European Molecular Biology Organization (EMBO) ALTF 750-2022Friedreich's Ataxia Research Alliance (FARA) FARA FellowshipMassachusetts General Hospital (MGH) ECOR FMD FellowshipMassachusetts General Hospital (MGH) Howard M. Goodman FellowshipMassachusetts General Hospital (MGH) Kayden-Lambert MGH Research Scholar Award 2023-2028National Science Foundation (NSF) 2020295403NCI NIH HHS DP2 CA281401NHGRI NIH HHS R35 HG010717NHGRI NIH HHS UM1 HG012010NHLBI NIH HHS P01 HL142494NIGMS NIH HHS R35 GM142553NINDS NIH HHS U54 NS115052Swiss National Science Foundation | National Center of Competence in Research Quantum Science and Technology (NCCR QSIT - Quantum Science and Technology) P180777U.S. Department of Health Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) P01-HL142494U.S. Department of Health Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1-HG012010U.S. Department of Health Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM142553U.S. Department of Health Human Services | NIH | NIH Office of the Director (OD) DP2-CA281401
6 · The paper itself

Abstract

Genome editing technologies based on DNA-dependent polymerases (DDPs) could offer several benefits compared with other types of editors to install diverse edits. Here, we develop click editing, a genome writing platform that couples the advantageous properties of DDPs with RNA-programmable nickases to permit the installation of a range of edits, including substitutions, insertions and deletions. Click editors (CEs) leverage the 'click'-like bioconjugation ability of HUH endonucleases with single-stranded DNA substrates to covalently tether 'click DNA' (clkDNA) templates encoding user-specifiable edits at targeted genomic loci. Through iterative optimization of the modular components of CEs and their clkDNAs, we demonstrate the ability to install precise genome edits with minimal indels in diverse immortalized human cell types and primary fibroblasts with precise editing efficiencies of up to ~30%. Editing efficiency can be improved by rapidly screening clkDNA oligonucleotides with various modifications, including repair-evading substitutions. Click editing is a precise and versatile genome editing approach for diverse biological applications.

Indexed as

DNA-Directed DNA PolymeraseEndonucleasesGene EditingClick ChemistryCRISPR-Cas SystemsGenome, HumanHumansDNA-Directed DNA PolymeraseEndonucleases

Identifiers

PMID39039307
PMCPMC11751136

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Registered trials

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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.