Evidence map›Paper›PMID 37533254›Full record

ReviewMolecular therapy : the journal of the American Society of Gene Therapy2023

Stowaways in the cargo: Contaminating nucleic acids in rAAV preparations for gene therapy.

Mark A Brimble, Stephen M Winston, Andrew M Davidoff

Open access · hybridAbstract readReview
In one paragraph

Review in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
11.0field-weighted citation impact, top 1% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Residual DNA impurities in AAV vectors-nature and transcription.Molecular therapy. Methods & clinical development · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Non-encapsidated miRNA contaminants found in AAV preparations.Molecular therapy. Methods & clinical development · 2024
    Article
  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

3 authors at 1 institution in 1 country.

Mark A BrimbleDepartment of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: mark.brimble@stjude.org.
Stephen M WinstonDepartment of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; St. Jude Children's Research Hospital Graduate School of Biomedical Sciences, 262 Danny Thomas Place, Memphis, TN 38105, 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 · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant AAV (rAAV) is the most used delivery vector for clinical gene therapy. However, many issues must be addressed before safer and more widespread implementation can be achieved. At present, efficacies are highly variable across trials and patients, and immune responses after treatment are widely reported. Although rAAV is capable of directly delivering gene-encoded therapeutic sequences, increased scrutiny of viral preparations for translational use have revealed contaminating nucleic acid species packaged within rAAV preparations. The introduction of non-therapeutic nucleic acids into a recipient patient adds to the risk burden, immunogenic or otherwise, of rAAV therapies. DNA from incomplete expression cassettes, portions of plasmids or vectors used to facilitate viral replication, and production cell line genomes all have the potential to be packaged within rAAV. Here, we review what is currently known about the profile, abundance, and post-treatment consequences of nucleic acid impurities within rAAV and cover strategies that have been developed to improve rAAV purity. Furthering our understanding of these aberrantly packaged DNA species will help to ensure the continued safe implementation of rAAV therapies as the number of patients treated with this modality increases.

Indexed as

DependovirusGenetic TherapyGenetic VectorsAnimalsDNA ContaminationGene Transfer TechniquesHumansNucleic AcidsNucleic AcidsAAVadeno-associated viruscontaminationgene therapyheterogeneitymanufacturingproduct-related-impuritiesQCrAAVvector production

Identifiers

PMID37533254
PMCPMC10556190
OpenAlexW4385486963

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.