Evidence map›Paper›PMID 30245471›Full record

ArticleMolecular therapy. Nucleic acids2018

Tissue-Dependent Expression and Translation of Circular RNAs with Recombinant AAV Vectors In Vivo.

Rita M Meganck, Erin K Borchardt, Ruth M Castellanos Rivera, Miranda L Scalabrino, Jeremy E Wilusz, William F Marzluff, Aravind Asokan

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Acta pharmaceutica Sinica. B · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Tumor-suppressive circRNAs in colorectal cancer spheroids and patients.Journal of the Chinese Medical Association : JCMA · 2026
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. The therapeutic potential of circular RNAs.Nature reviews. Genetics · 2025
    Review
  15. Review
  16. Review
  17. An Overview of Circular RNAs.Advances in experimental medicine and biology · 2025
    Review
  18. The Internal Ribosome Entry Site in Circular RNAs.Advances in experimental medicine and biology · 2025
    Review
  19. Review
  20. Challenges and Future Prospectives in Circular RNA Investigation.Advances in experimental medicine and biology · 2025
    Review

33 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Rita M MeganckCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Erin K BorchardtCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Ruth M Castellanos RiveraGene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Miranda L ScalabrinoGene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Jeremy E WiluszDepartment of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
William F MarzluffCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Aravind AsokanCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA. Electronic address: aravind.asokan@duke.edu.
University of North Carolina at Chapel Hill · USUniversity of Pennsylvania · US

Funding

Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
RE-ENGINEERING AAV GENOME PACKAGINGR01GM127708 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2018 to 2021
$2.0M
CircRNAs and CNS Gene TransferR01NS099371 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL089221NIGMS NIH HHS R01 GM127708NIGMS NIH HHS T32 GM007092NINDS NIH HHS R01 NS099371
6 · The paper itself

Abstract

Circular RNAs (circRNAs) are long-lived, covalently closed RNAs that are abundantly expressed and evolutionarily conserved across eukaryotes. Possible functions ranging from microRNA (miRNA) and RNA binding protein sponges to regulators of transcription and translation have been proposed. Here we describe the design and characterization of recombinant adeno-associated viral (AAV) vectors packaging transgene cassettes containing intronic sequences that promote backsplicing to generate circularized RNA transcripts. Using a split GFP transgene, we demonstrate the capacity of vectors containing different flanking intronic sequences to efficiently drive persistent circRNA formation in vitro. Further, translation from circRNA is efficiently driven by an internal ribosomal entry site (IRES). Upon injecting AAV vectors encoding circRNA in mice, we observed robust transgene expression in the heart, but low transduction in the liver for the intronic elements tested. Expression in the murine brain was restricted to astrocytes following systemic or intracranial administration, while intravitreal injection in the eye yielded robust transgene expression across multiple retinal cell layers. These results highlight the potential for exploiting AAV-based circRNA expression to study circRNA function and tissue-specific regulation in animal models, as well as development of therapeutic platforms using this approach.

Indexed as

adeno-associated viruscircular RNAgene therapy

Identifiers

PMID30245471
PMCPMC6154398
OpenAlexW2885493792

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.