Evidence map›Paper›PMID 42236706›Full record

ArticleNature communications2026

Multimodal control of Cas13d activity through domain insertion at an allosteric hotspot.

Liyuan Zhu, Long T Nguyen, Alexandra G Bell, Tom Krebel, Kara M Gillmann, Qinhao Cao, Harrison Oatman, Jack Hariri, Andreas Möglich, Cameron Myhrvold and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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

11 authors.

Liyuan Zhu *Department of Chemistry, Princeton University, Princeton, NJ, USA.
Long T Nguyen *Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ, USA.
Alexandra G BellDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0009-0001-2036-0455
Tom KrebelPhotobiochemistry Group, Department of Chemistry, University of Bayreuth, Bayreuth, Germany.ORCID http://orcid.org/0009-0001-9222-8453
Kara M GillmannDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Qinhao CaoDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Harrison OatmanLewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-2699-6374
Jack HaririDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Andreas MöglichPhotobiochemistry Group, Department of Chemistry, University of Bayreuth, Bayreuth, Germany.ORCID http://orcid.org/0000-0002-7382-2772
Cameron MyhrvoldDepartment of Chemistry, Princeton University, Princeton, NJ, USA. cmyhrvol@princeton.edu.ORCID http://orcid.org/0000-0002-8971-184X
Jared E ToettcherOmenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ, USA. toettcher@princeton.edu.ORCID http://orcid.org/0000-0002-1546-4030

Funding

ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
A new class of biosensors for detecting signaling dynamics without live-cell microscopyR01GM144362 · NIGMS · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2022 to 2025
$1.3M
Optogenetics and biosensors for dissecting cellular decision-makingR35GM164185 · NIGMS · PRINCETON UNIVERSITY · PI Jared E Toettcher · 2026 to 2026
$369k
NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R01 GM144362NIGMS NIH HHS R35 GM164185U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM144362
6 · The paper itself

Abstract

CRISPR-Cas13d RNA nucleases are powerful tools for programmable RNA targeting. A light-controlled RNA nuclease could be transformative by enabling researchers to selectively knock down transcripts at desired positions in a cell or tissue or at timepoints of interest. Here, we develop a set of RfxCas13d tools that can be multimodally controlled by either light or small molecule addition. By screening an RfxCas13d library containing insertions of the AsLOV2 photoswitchable domain, we identify an OptoCas13d-off variant that induced target RNA cleavage in the dark and switched to an inactive state under blue light. We show that the same allosteric hotspot can be exploited to generate an OptoCas13d-on with an inverted light response and a ChemoCas13d that is activated by rapamycin analogs, enabling knockdown of endogenous mRNA and protein targets. Overall, our study shows that engineered allostery can produce stimulus-controlled Cas13d variants to modulate RNA with high spatial and temporal precision.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsAllosteric RegulationBlue LightHEK293 CellsHumansProtein DomainsSirolimusCRISPR-Associated ProteinsSirolimus

Identifiers

PMID42236706
PMCPMC13396516

What OpenQuestion holds

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LicenceCC BY
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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.