Evidence map›Paper›PMID 35211640›Full record

ArticleMolecular therapy. Methods & clinical development2022

Preventing packaging of translatable P5-associated DNA contaminants in recombinant AAV vector preps.

Mark A Brimble, Pei-Hsin Cheng, Stephen M Winston, Isaiah L Reeves, Aisha Souquette, Yunyu Spence, Junfang Zhou, Yong-Dong Wang, Christopher L Morton, Marcus Valentine and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Residual DNA impurities in AAV vectors-nature and transcription.Molecular therapy. Methods & clinical development · 2025
    Article
  8. Article
  9. Article
  10. AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Stowaways in the cargo: Contaminating nucleic acids in rAAV preparations for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Review
  20. 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

14 authors at 3 institutions in 2 countries.

Mark A BrimbleDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Pei-Hsin ChengDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Stephen M WinstonDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Isaiah L ReevesDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Aisha SouquetteDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yunyu SpenceDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Junfang ZhouDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Yong-Dong WangDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Christopher L MortonDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Marcus ValentineCytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Paul G ThomasDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Amit C NathwaniDepartment of Haematology, University College London (UCL) Cancer Institute, London WC1E 6DD, UK.
John T GrayVertex Cell and Genetic Therapies, Vertex Pharmaceuticals, Boston, MA 02210, USA.
Andrew M DavidoffDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
St. Jude Children's Research Hospital · USThe Royal Free Hospital · GBVertex Pharmaceuticals (United States) · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
NCI NIH HHS P30 CA021765
6 · The paper itself

Abstract

Recombinant adeno-associated virus (rAAV) vectors are increasingly being used for clinical gene transfer and have shown great potential for the treatment of several monogenic disorders. However, contaminant DNA from producer plasmids can be packaged into rAAV alongside the intended expression cassette-containing vector genome. The consequences of this are unknown. Our analysis of rAAV preps revealed abundant contaminant sequences upstream of the AAV replication (Rep) protein driving promoter, P5, on the Rep-Cap producer plasmid. Characterization of P5-associated contaminants after infection showed transfer, persistence, and transcriptional activity in AAV-transduced murine hepatocytes, in addition to

Indexed as

Adeno-associated viruscontaminationgene therapyP5rAAVvectorologyviral manufacturing

Identifiers

PMID35211640
PMCPMC8829444
OpenAlexW4205517561

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.