Evidence map›Paper›PMID 39693429›Full record

ArticleScience advances2024

Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision.

Carolyn Shembrey, Ray Yang, Joshua Casan, Wenxin Hu, Honglin Chen, Gurjeet J Singh, Teresa Sadras, Krishneel Prasad, Jake Shortt, Ricky W Johnstone and 3 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. A Modular and Programmable Cas13d Platform for RNA Single Nucleotide Variant Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. 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

13 authors.

Carolyn ShembreyRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0003-3175-8925
Ray YangRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0009-0006-8478-3656
Joshua CasanRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0002-4322-8561
Wenxin HuRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
Honglin ChenRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
Gurjeet J SinghRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.
Teresa SadrasRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0001-9048-9580
Krishneel PrasadRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0003-1085-9591
Jake ShorttRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0003-3185-6488
Ricky W JohnstoneRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0001-7053-9237
Joseph A TrapaniRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0003-0983-1532
Paul G EkertRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0002-2976-8617
Mohamed FarehRosie Lew Program in Immunotherapy and Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia.ORCID 0000-0001-9551-8213

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single-nucleotide variants (SNVs) are extremely prevalent in human cancers, although most of these remain clinically unactionable. The programmable RNA nuclease CRISPR-Cas13 has been deployed to specifically target oncogenic RNAs. However, silencing oncogenic SNVs with single-base precision remains extremely challenging due to the intrinsic mismatch tolerance of Cas13. Here, we show that introducing synthetic mismatches at precise positions of the spacer sequence enables de novo design of guide RNAs [CRISPR RNAs (crRNAs)] with strong preferential silencing of point-mutated transcripts. We applied these design principles to effectively silence the oncogenic

Indexed as

CRISPR-Cas SystemsBase Pair MismatchGene EditingGene SilencingGTP PhosphohydrolasesHumansMembrane ProteinsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)RNA, Guide, CRISPR-Cas SystemsRNA, NeoplasmBRAF protein, humanGTP PhosphohydrolasesKRAS protein, humanMembrane ProteinsNRAS protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)RNA, Guide, CRISPR-Cas SystemsRNA, Neoplasm

Identifiers

PMID39693429
PMCPMC11654686

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LicenceCC BY-NC
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Registered trials

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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.