Evidence map›Paper›PMID 42168701›Full record

ArticleNature biotechnology2026

AI-guided redesign of laboratory-evolved reverse transcriptases enhances prime editing.

Y Allen Tao, Holt A Sakai, Allen Y Jiang, Nicholas A Krasnow, Vasilii S Vaganov, Brian Shim, Zachary Barsdale, Smriti Pandey, Nouraiz Ahmed, Man Na and 7 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 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. bioRxiv : the preprint server for biology · 2026
    Article
  3. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Wheat's Up with CRISPR-Cas-Current Advances, Obstacles and Perspectives.International journal of molecular sciences · 2026
    Review
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

17 authors.

Y Allen Tao *Merkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Holt A Sakai *Merkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9338-1484
Allen Y Jiang *Merkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9826-5976
Nicholas A Krasnow *Merkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4131-1855
Vasilii S VaganovMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brian ShimMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zachary BarsdaleMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1196-8669
Smriti PandeyMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5461-5690
Nouraiz AhmedMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Man NaMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0002-8892-7881
Ting-Wei LiaoMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Keyede OyeMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ana CristianMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Emily ZhangMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9053-1336
Joy A XuMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0007-7648-4805
Mattijs BulcaenMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, 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
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
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB031172 · NIBIB · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2021 to 2024
$2.5M
NHLBI NIH HHS R01 HL156647U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) RM1HG009490U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB031172U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM118062
6 · The paper itself

Abstract

Although protein engineering and laboratory evolution have been used to optimize prime editors, we show that previous changes that improve prime editor efficiency also compromise protein stability and expression level, limiting performance. To address these limitations, we apply structure-informed artificial intelligence-guided methods such as the inverse-folding network ProteinMPNN to redesign the reverse transcriptase (RT) domains of engineered and evolved prime editors while preserving regions essential for catalysis. Redesigned RTs are extensively mutated, with 30-163 amino acid substitutions, and exhibit enhanced folding stability and soluble expression and up to twofold higher intracellular prime editor protein levels following mRNA delivery. Redesigned PE8 prime editors demonstrate enhanced editing efficiencies across multiple ex vivo contexts, including in several human primary cell types and via several delivery modalities. In mice, editing efficiency is up to 2.9-fold higher than that of state-of-the-art PE6, PE7 and PEmax prime editors. These findings demonstrate a generalizable approach for augmenting laboratory evolution to improve genome editing agents.

Identifiers

PMID42168701

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.