Evidence map›Paper›PMID 41757025›Full record

ArticlebioRxiv : the preprint server for biology2026

Mechanistic machine learning enables interpretable and generalizable 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 readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Alvin HsuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Peter J ChenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Angus H LiMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.ORCID 0000-0002-7330-465X
Colin F HemezMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Xin D GaoMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Markus TerreyRare Disease Translational Center, The Jackson Laboratory; Bar Harbor, ME, 04609, USA.
Charlie NelsonRare Disease Translational Center, The Jackson Laboratory; Bar Harbor, ME, 04609, USA.
Vijay SelvamRare Disease Translational Center, The Jackson Laboratory; Bar Harbor, ME, 04609, USA.
Ana CristianMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Amber N McElroyDepartment of Pediatrics, University of Minnesota Medical School; Minneapolis, MN, 55455, USA.
Benjamin J SteinbeckDepartment of Pediatrics, University of Minnesota Medical School; Minneapolis, MN, 55455, USA.
Gandhar K MahadeshwarMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Smriti PandeyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Zachary BarsdaleMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Paul Z ChenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Alexander A SousaMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Holt A SakaiMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Rachel A SilversteinCenter for Genomic Medicine, Massachusetts General Hospital; Boston, MA, 02114, USA.ORCID 0000-0001-5724-2252
Ilias MoradMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.
Ryan K KruegerJohn A. Paulson School of Engineering and Applied Sciences, Harvard University; Cambridge, MA, 02138, USA.
Max W ShenMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.ORCID 0000-0002-4226-1861
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital; Boston, MA, 02114, USA.ORCID 0000-0002-5469-0655
Cathleen M LutzRare Disease Translational Center, The Jackson Laboratory; Bar Harbor, ME, 04609, USA.
Jakub TolarDepartment of Pediatrics, University of Minnesota Medical School; Minneapolis, MN, 55455, USA.
Bruce R BlazarDepartment of Pediatrics, University of Minnesota Medical School; Minneapolis, MN, 55455, USA.
Mark J OsbornDepartment of Pediatrics, University of Minnesota Medical School; Minneapolis, MN, 55455, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT; Cambridge, MA, 02142, USA.

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
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
PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Matthias Nahrendorf · 2019 to 2026
$19.5M
The Jackson Laboratory Center for Precision GeneticsU54OD030187 · OD · JACKSON LABORATORY · PI Stephen A Murray · 2020 to 2026
$17.2M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Skin-targeted Cell Therapy for Recessive Dystrophic Epidermolysis BullosaR01AR063070 · NIAMS · UNIVERSITY OF MINNESOTA · PI Mark J Osborn, Jakub Tolar · 2013 to 2026
$4.5M
Nongenotoxic conditioning for gene therapy and allogeneic transplantation in Fanconi anemiaR01HL147324 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Bruce R Blazar, HANS-PETER KIEM · 2020 to 2026
$4.1M
Scalable Development of Custom Genome Editing TechnologiesDP2CA281401 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2022 to 2025
$2.5M
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
Interrogation of Neurological Pathologies Associated with Mutations in Kif1aR61NS133266 · NINDS · JACKSON LABORATORY · PI LUTZ, CATHLEEN M · 2023 to 2024
$647k
NCI NIH HHS DP2 CA281401NCI NIH HHS P01 CA065493NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS P01 HL142494NHLBI NIH HHS R01 HL147324NIAID NIH HHS U01 AI142756NIAMS NIH HHS R01 AR063070NIBIB NIH HHS R01 EB022376NIGMS NIH HHS R35 GM118062NIH HHS U54 OD030187NINDS NIH HHS R61 NS133266
6 · The paper itself

Abstract

Although prime editing (PE) can effect virtually any specified local change to genomic DNA in living systems, its efficient application currently requires extensive optimization of prime editing guide RNA (pegRNA) sequences. We present OptiPrime, a machine learning model of PE efficiency based on our current understanding of the mechanism of prime editing. OptiPrime achieves state-of-the-art accuracy on PE efficiency prediction and also enables prediction of nicking guide RNA (PE3) and dual pegRNA (twinPE) outcomes. We validated that OptiPrime has learned the determinants of mammalian mismatch repair (MMR), and is therefore well suited for nominating MMR-evasive silent edits that improve PE efficiency. We demonstrate the utility of OptiPrime in a variety of prospective therapeutic contexts, including in primary human and mouse cells. Finally, we show how OptiPrime can be used to achieve highly streamlined and efficient

Identifiers

PMID41757025
PMCPMC12934823

What Socratic 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 Socratic graph.