Evidence map›Paper›PMID 41219485›Full record

ArticleNature biotechnology2025

A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording.

Troy A McDiarmid, Megan L Taylor, Wei Chen, Florence M Chardon, Junhong Choi, Hanna Liao, Xiaoyi Li, Haedong Kim, Jean-Benoît Lalanne, Tony Li and 7 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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  3. Article
  4. Base editors model mitochondrial disease.Nature biotechnology · 2026
    Article
  5. Article
  6. Article
  7. 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

17 authors.

Troy A McDiarmid *Department of Genome Sciences, University of Washington, Seattle, WA, USA. troym13@uw.edu.ORCID http://orcid.org/0000-0002-4893-9733
Megan L Taylor *Department of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0009-0002-2511-1498
Wei ChenDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5255-4166
Florence M ChardonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Junhong ChoiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-9291-5977
Hanna LiaoDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Xiaoyi LiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Haedong KimDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3589-0042
Jean-Benoît LalanneDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Tony LiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jenny F NathansDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-0276-734X
Beth K MartinDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9661-014X
Jordan KnuthSeattle Hub for Synthetic Biology, Seattle, WA, USA.ORCID http://orcid.org/0009-0007-0176-7093
Alessandro L V CoradiniSeattle Hub for Synthetic Biology, Seattle, WA, USA.
Jesse M GraySeattle Hub for Synthetic Biology, Seattle, WA, USA.
Sudarshan PinglayDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. shendure@uw.edu.ORCID http://orcid.org/0000-0002-1516-1865

Funding

Supplement for Center for Synthetic Regulatory Genomics: Building CACNA1C alleles associated with Neuropsychiatric DisordersRM1HG009491 · NHGRI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jef D BOEKE · 2018 to 2026
$20.9M
Versatile, exponentially scalable methods for single cell molecular profilingR01HG010632 · NHGRI · UNIVERSITY OF WASHINGTON · PI Jay Ashok Shendure, Bruce Colston Trapnell · 2019 to 2026
$5.9M
Dissecting the logic of mammalian gene regulation using synthetic biology and single-cell sequencingDP5OD036167 · OD · UNIVERSITY OF WASHINGTON · PI Sudarshan Pinglay · 2023 to 2026
$1.9M
Molecular recording to understand the determinants of cell fate transitions in early developmentR00HG012973 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI Junhong Choi · 2024 to 2026
$747k
Molecular recording to understand the determinants of cell fate transitions in early developmentK99HG012973 · NHGRI · UNIVERSITY OF WASHINGTON · PI CHOI, JUNHONG · 2023 to 2023
$114k
Howard Hughes Medical InstituteNHGRI NIH HHS K99 HG012973NHGRI NIH HHS R00 HG012973NHGRI NIH HHS R01 HG010632NHGRI NIH HHS RM1 HG009491NIH HHS DP5 OD036167U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG010632
6 · The paper itself

Abstract

A standardized 'parts list' of sequences for genetic engineering of microbes has been indispensable to progress in synthetic biology, but few analogous parts exist for mammalian systems. Here we design libraries of extant, ancestral, mutagenized or miniaturized variants of polymerase III promoters and guide RNA (gRNA) scaffolds and quantify their abilities to mediate precise edits to the mammalian genome through multiplex prime editing. We identify thousands of parts for reproducible editing in human and mouse cell lines, including hundreds with greater activity than commonly used sequences. Saturation mutagenesis screens identify tolerated sequence variants that further enhance sequence diversity. In an application to molecular recording, we design a 'ten key' array that, in mammalian cells, achieves balanced activity of pegRNAs as predicted by the activity of the component parts. The data reported here will aid the design of synthetic loci encoding arrays of gRNAs exhibiting predictable, differentiated levels of activity for applications in multiplexed perturbation, biological recorders and complex genetic circuits.

Identifiers

PMID41219485
PMCPMC13355316

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.