Evidence map›Paper›PMID 42587136›Full record

ArticleNature biotechnology2026

Mechanistic machine learning for prediction of prime editing outcomes.

Alvin Hsu, Peter J Chen, Angus H Li, Colin F Hemez, Xin D Gao, Markus Terrey, Charlie Nelson, Vijay Selvam, Ana Cristian, Amber N McElroy and 17 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Alvin Hsu *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4034-2788
Peter J Chen *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1094-7180
Angus H Li *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7330-465X
Colin F HemezMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Xin D GaoMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2917-2060
Markus TerreyRare Disease Translational Center, The Jackson Laboratory, Bar Harbor, ME, USA.
Charlie NelsonRare Disease Translational Center, The Jackson Laboratory, Bar Harbor, ME, USA.ORCID http://orcid.org/0000-0002-2463-2155
Vijay SelvamRare Disease Translational Center, The Jackson Laboratory, Bar Harbor, ME, USA.
Ana CristianMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Amber N McElroyDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-4169-0015
Benjamin J SteinbeckDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-6444-8643
Gandhar K MahadeshwarMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3181-7262
Smriti PandeyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5461-5690
Zachary BarsdaleMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1196-8669
Paul Z ChenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5261-1610
Alexander A SousaMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Holt A SakaiMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9338-1484
Rachel A SilversteinCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Ilias MoradORCID http://orcid.org/0009-0000-0597-4945
Ryan K KruegerJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Max W ShenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5469-0655
Cathleen M LutzRare Disease Translational Center, The Jackson Laboratory, Bar Harbor, ME, USA.
Jakub TolarDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-0957-4380
Bruce R BlazarDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Mark J OsbornDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, 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/0000-0002-9943-7557

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
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
Howard Hughes Medical Institute (HHMI) Liu investigatorshipU.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) RM1HG009490U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U01AI142756U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB022376U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM118062
6 · The paper itself

Abstract

Prime editing (PE) can make specific local changes to genomic DNA in living systems but its efficient application currently requires extensive optimization of PE guide RNA (pegRNA) sequences. Here we present OptiPrime, a machine learning model of PE efficiency based on current understanding of PE mechanisms. OptiPrime achieves state-of-the-art accuracy on PE efficiency prediction and enables prediction of nicking guide RNA (PE3) and dual pegRNA (twinPE) outcomes. We validate that OptiPrime has learned the determinants of mammalian mismatch repair (MMR) and is well suited for nominating MMR-evasive silent edits that improve PE efficiency. We demonstrate the use of OptiPrime in a variety of prospective therapeutic contexts in primary human and mouse cells. Lastly, we show that OptiPrime can be used to achieve streamlined and efficient in vivo correction of a pathogenic mutation in the brain of a mouse model of KIF1A-associated neurological disorder. We provide a webserver for OptiPrime ( https://optipri.me/ ) as a community resource.

Identifiers

PMID42587136

What Socratic holds

Textmetadata
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.