Evidence map›Paper›PMID 42162366›Full record

ArticleNature biotechnology2026

Directed evolution of small RNA-stabilizing motifs that improve prime-editing efficiency.

Holt A Sakai, Sarah E Pierce, Allen Y Jiang, Ana Cristian, Meirui An, Chae Rin Kim, Nouraiz Ahmed, Colin F Hemez, Y Allen Tao, Emily Zhang and 2 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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

12 authors.

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
Sarah E Pierce *Merkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Allen Y JiangMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9826-5976
Ana CristianMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Meirui AnMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4006-8670
Chae Rin KimDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Nouraiz AhmedMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Colin F HemezMerkin Institute of Transformative Technologies in Healthcare, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Y Allen TaoMerkin 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
Sophia J WuMerkin 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
Howard Hughes Medical Institute (HHMI) Liu investigatorshipNHLBI 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 General Medical Sciences (NIGMS) R35GM118062
6 · The paper itself

Abstract

The performance of prime-editing (PE) systems has been improved by systematic engineering of their protein and small RNA components but the structured RNA motifs appended to the 3' end of PE guide RNAs (pegRNAs)-a key determinant of pegRNA stability and editing efficiency-have not been extensively studied. We introduce PE-PRISM, a high-throughput pooled screen to identify and optimize these 3' RNA motifs in human cells. Here, using PE-PRISM, we evaluated 2,858 RNA motifs across four iterative libraries, including natural and engineered pseudoknots, G-quadruplexes and reverse transcriptase recruitment elements. We applied structure-guided mutagenesis and combinatorial variant screening to refine hits, culminating in the engineered and evolved pseudoknot variants tevo2.0, eHAV and eSBRMV1-A. In a screen correcting 847 pathogenic ClinVar variants, the top-performing motifs improved PE efficiency over the widely used tevopreQ

Identifiers

PMID42162366

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.