Evidence map›Paper›PMID 39990302›Full record

ArticlebioRxiv : the preprint server for biology2025

Mutational scanning of TnpB reveals latent activity for genome editing.

Brittney W Thornton, Rachel F Weissman, Jorge E Rodriguez, Ryan V Tran, Brenda T Duong, Cynthia I Terrace, Ugrappa Nagalakshmi, George Austin, Evan D Groover, Flora Zhiqi Wang and 7 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Brittney W ThorntonDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0009-0000-5615-2853
Rachel F WeissmanDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0002-1806-6564
Jorge E RodriguezDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0002-3177-2586
Ryan V TranDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID 0009-0002-4648-7785
Brenda T DuongDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID 0009-0001-5529-8508
Cynthia I TerraceDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0003-1578-9000
Ugrappa NagalakshmiDepartment of Plant Biology, University of California Davis, Davis, CA, USA.ORCID 0000-0001-7981-5031
George AustinInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Evan D GrooverInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0001-9737-1796
Flora Zhiqi WangInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID 0009-0006-2874-0942
Jung-Un ParkDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0002-0269-7142
Viktoriya GeorgievaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0009-0001-5843-726X
Julia TartagliaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0002-3399-1926
Myeong-Je ChoInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Savithramma P Dinesh-KumarDepartment of Plant Biology, University of California Davis, Davis, CA, USA.ORCID 0000-0001-5738-316X
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0001-9161-999X
David F SavageDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0003-0042-2257

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$35.7M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Danielle L Swaney · 2018 to 2026
$21.4M
Resource Core II: In Vivo CoreU19NS132303 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NIREN MURTHY · 2023 to 2026
$19.7M
Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0M
Cas9 RNP delivery to immune cells in vivo via molecular targetingUH3AI150552 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI DOUDNA, JENNIFER A, WILSON, ROSS C · 2022 to 2022
$1.3M
Engineering CRISPR-Cas proteins for conditional and robust interrogation of the genomeR01GM127463 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SAVAGE, DAVID FRANK · 2019 to 2022
$1.2M
Targeted Delivery of Cas9 to Lung Epithelial Cells using Enveloped Delivery VehiclesR21HL173710 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI DOUDNA, JENNIFER A · 2024 to 2025
$520k
NHLBI NIH HHS R21 HL173710NIAID NIH HHS U01 AI142817NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI171110NIAID NIH HHS U54 AI170792NIAID NIH HHS UH3 AI150552NIGMS NIH HHS R01 GM127463NINDS NIH HHS U19 NS132303
6 · The paper itself

Abstract

TnpB is a diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Due to their small size and putative evolutionary relationship to CRISPR-Cas12, TnpB enzymes hold significant potential for genome editing. However, most TnpBs lack robust gene editing activity, and unbiased profiling of mutational effects on editing activity has not been explored. Here, we mapped comprehensive sequence-function landscapes of a TnpB ribonucleoprotein and discovered many activating mutations in both the protein and RNA. One- and two-position RNA mutants outperform existing variants, highlighting the utility of systematic RNA scaffold mutagenesis. Leveraging the protein's mutational landscape, we identified enhanced TnpB variants from a combinatorial library of activating mutations. These variants enhanced editing in human cells,

Identifiers

PMID39990302
PMCPMC11844463

What OpenQuestion holds

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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 OpenQuestion graph.