Evidence map›Paper›PMID 38485709›Full record

ArticleNature communications2024

Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing.

David N Fiflis, Nicolas A Rey, Harshitha Venugopal-Lavanya, Beatrice Sewell, Aaron Mitchell-Dick, Katie N Clements, Sydney Milo, Abigail R Benkert, Alan Rosales, Sophia Fergione and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Spligation enables programmable chimeric RNA generation in living cells.bioRxiv : the preprint server for biology · 2026
    Article
  7. Review
  8. The "cutting edge" of non-canonical RNA splicing.Frontiers in molecular biosciences · 2026
    Review
  9. Review
  10. Article
  11. RNAMolecular therapy. Nucleic acids · 2025
    Article
  12. Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  13. Review
  14. Review
  15. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  16. Review
  17. Precision Transcriptome Editing.ACS synthetic biology · 2024
    Review
  18. Review
  19. Review
  20. Review
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 at 1 institution in 1 country.

David N FiflisDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID 0000-0003-3411-8560
Nicolas A ReyDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.ORCID 0009-0009-2703-8141
Harshitha Venugopal-LavanyaDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.ORCID 0009-0007-0262-4609
Beatrice SewellDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Aaron Mitchell-DickDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Katie N ClementsDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Sydney MiloDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Abigail R BenkertDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Alan RosalesDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Sophia FergioneDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Aravind AsokanDepartment of Biomedical Engineering, Duke University, Durham, NC, USA. aravind.asokan@duke.edu.ORCID 0000-0001-5563-4877
Duke University · US

Funding

Evaluation of adeno-associated viral (AAV) mediated gene replacement therapy as a therapeutic option for SLC25A4 deficiencyF32HL167559 · NHLBI · DUKE UNIVERSITY · PI BENKERT, ABIGAIL · 2023 to 2024
$160k
NHLBI NIH HHS F32 HL167559
6 · The paper itself

Abstract

Type VI CRISPR enzymes have been developed as programmable RNA-guided Cas proteins for eukaryotic RNA editing. Notably, Cas13 has been utilized for site-targeted single base edits, demethylation, RNA cleavage or knockdown and alternative splicing. However, the ability to edit large stretches of mRNA transcripts remains a significant challenge. Here, we demonstrate that CRISPR-Cas13 systems can be repurposed to assist trans-splicing of exogenous RNA fragments into an endogenous pre-mRNA transcript, a method termed CRISPR Assisted mRNA Fragment Trans-splicing (CRAFT). Using split reporter-based assays, we evaluate orthogonal Cas13 systems, optimize guide RNA length and screen for optimal trans-splicing site(s) across a range of intronic targets. We achieve markedly improved editing of large 5' and 3' segments in different endogenous mRNAs across various mammalian cell types compared to other spliceosome-mediated trans-splicing methods. CRAFT can serve as a versatile platform for attachment of protein tags, studying the impact of multiple mutations/single nucleotide polymorphisms, modification of untranslated regions (UTRs) or replacing large segments of mRNA transcripts.

Indexed as

CRISPR-Cas SystemsGene EditingAnimalsMammalsRNARNA, Guide, CRISPR-Cas SystemsRNA, MessengerTrans-SplicingRNARNA, Guide, CRISPR-Cas SystemsRNA, Messenger

Identifiers

PMID38485709
PMCPMC10940283
OpenAlexW4392818398

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.