Evidence map›Paper›PMID 40730819›Full record

ArticleNature communications2025

Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox.

Megan D Schertzer, Andrew Stirn, Keren Isaev, Laura Pereira, Stella H Park, Anjali Das, Aline Réal, Erin D Jeffery, Claire Harbison, Hans-Hermann Wessels and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Orthrus: Towards Evolutionary and Functional RNA Foundation Models.bioRxiv : the preprint server for biology · 2025
    Article
  9. Approaches to probe and perturb long noncoding RNA functions in diseases.Current opinion in genetics & development · 2024
    Review
  10. RNA structure modulates Cas13 activity and enables mismatch detection.bioRxiv : the preprint server for biology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Megan D SchertzerNew York Genome Center, New York, NY, USA. megan.schertzer@gmail.com.ORCID http://orcid.org/0000-0003-4997-8221
Andrew Stirn *New York Genome Center, New York, NY, USA.
Keren Isaev *New York Genome Center, New York, NY, USA.
Laura PereiraNew York Genome Center, New York, NY, USA.
Stella H ParkNew York Genome Center, New York, NY, USA.ORCID http://orcid.org/0009-0008-0933-8602
Anjali DasNew York Genome Center, New York, NY, USA.
Aline RéalNew York Genome Center, New York, NY, USA.
Erin D JefferyDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0001-9511-7719
Claire HarbisonNew York Genome Center, New York, NY, USA.
Hans-Hermann WesselsNew York Genome Center, New York, NY, USA.
Gloria M SheynkmanDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-4223-9947
Neville E SanjanaNew York Genome Center, New York, NY, USA.
David A KnowlesNew York Genome Center, New York, NY, USA. daknowles@nygenome.org.ORCID http://orcid.org/0000-0002-7408-146X

Funding

Predicting the functional impact of non-coding mutations using patient-specific gene regulatory networksR01CA218668 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI EKTA KHURANA, Neville Sanjana · 2018 to 2026
$4.7M
Multiscale genome engineering to map cis-regulatory variants in human and mouseR01HG012790 · NHGRI · NEW YORK GENOME CENTER · PI Tuuli Lappalainen, Dan Littman · 2023 to 2026
$4.5M
In situ functional genomics to understand transcriptional regulationDP2HG010099 · NHGRI · NEW YORK GENOME CENTER · PI SANJANA, NEVILLE · 2017 to 2022
$4.4M
Enhancing Susceptibility of HIV Reservoirs to CTL Through a Discovery to Translational ApproachR01AI176601 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI R. Brad Jones, Neville Sanjana · 2023 to 2026
$3.3M
LTBR CARs as next-generation therapies for R/R lymphomaR01CA279135 · NCI · NEW YORK GENOME CENTER · PI Catherine Sibyl Diefenbach, Neville Sanjana · 2023 to 2026
$3.2M
Scalable multi-ancestry functional genomics of blood traits and cardiovascular diseaseR01HL168247 · NHLBI · NEW YORK GENOME CENTER · PI Neville Sanjana · 2024 to 2026
$2.4M
Uncovering the functional diversification mechanisms of transcription factor isoforms involved in stem cell differentiationR35GM142647 · NIGMS · UNIVERSITY OF VIRGINIA · PI SHEYNKMAN, GLORIA · 2021 to 2025
$2.1M
A CRISPR/Cas13 approach for identifying individual transcript isoform function in cancerR21CA272345 · NCI · NEW YORK GENOME CENTER · PI KNOWLES, DAVID ARTHUR · 2022 to 2023
$699k
Measuring allele and isoform-specific RBP binding to improve predictive models of RNA splicingF32GM142213 · NIGMS · NEW YORK GENOME CENTER · PI SCHERTZER, MEGAN · 2021 to 2022
$134k
NCI NIH HHS R01 CA218668NCI NIH HHS R01 CA279135NCI NIH HHS R21 CA272345NHGRI NIH HHS DP2 HG010099NHGRI NIH HHS R01 HG012790NHLBI NIH HHS R01 HL168247NIAID NIH HHS R01 AI176601NIGMS NIH HHS F32 GM142213NIGMS NIH HHS R35 GM142647U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01AI176601U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA272345U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) DP2HG010099U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) F32GM142213
6 · The paper itself

Abstract

Pre- and post-transcriptional mechanisms, including alternative promoters, termination signals, and splicing, play essential roles in diversifying protein output by generating distinct RNA and protein isoforms. Two major challenges in characterizing the cellular function of alternative isoforms are the lack of experimental methods to specifically and efficiently modulate isoform expression and computational tools for complex experimental design and analysis. To address these gaps, we develop and methodically test an isoform-specific knockdown strategy which pairs the RNA-targeting CRISPR/Cas13d system with guide RNAs that span exon-exon junctions. In parallel, we provide computational tools for experimental design and analysis. In this study, we demonstrate that junction-targeting achieves robust and isoform-specific RNA knockdown across diverse alternative isoform events, genes, and cell types.

Indexed as

Computational BiologyCRISPR-Cas SystemsGene Knockdown TechniquesRNAAlternative SplicingExonsHEK293 CellsHumansProtein IsoformsRNA, Guide, CRISPR-Cas SystemsProtein IsoformsRNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID40730819
PMCPMC12307810

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.