Evidence map›Paper›PMID 31909084›Full record

ArticleMolecular therapy. Methods & clinical development2020

Cross-Packaging and Capsid Mosaic Formation in Multiplexed AAV Libraries.

Pauline F Schmit, Simon Pacouret, Eric Zinn, Elizabeth Telford, Fotini Nicolaou, Frédéric Broucque, Eva Andres-Mateos, Ru Xiao, Magalie Penaud-Budloo, Mohammed Bouzelha and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. AAV capsid sites breakdown: large protein insertions impact on vector dynamics.Frontiers in bioengineering and biotechnology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Multiparametric domain insertional profiling of adeno-associated virus VP1.Molecular therapy. Methods & clinical development · 2023
    Article
  11. Review
  12. Article
  13. AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  14. Viral Tools for Neural Circuit Tracing.Neuroscience bulletin · 2022
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. 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 6 institutions in 2 countries.

Pauline F SchmitGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Simon PacouretGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Eric ZinnGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Elizabeth TelfordGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Fotini NicolaouGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Frédéric BroucqueINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Eva Andres-MateosGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Ru XiaoGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Magalie Penaud-BudlooINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Mohammed BouzelhaINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Nicolas JaulinINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Oumeya AdjaliINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Eduard AyusoINSERM UMR1089, University of Nantes, Centre Hospitalier Universitaire, Nantes, France.
Luk H VandenbergheGrousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
Smith-Kettlewell Eye Research Institute · USInserm · FRCentre Hospitalier Universitaire de Nantes · FRMassachusetts Eye and Ear Infirmary · USInnovative Genomics Institute · USNantes Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Generation and screening of libraries of adeno-associated virus (AAV) variants have emerged as a powerful method for identifying novel capsids for gene therapy applications. For the majority of libraries, vast population diversity requires multiplexed production, in which a library of inverted terminal repeat (ITR)-containing plasmid variants is transfected together into cells to generate the viral library. This process has the potential to be confounded by cross-packaging and mosaicism, in which particles are comprised of genomes and capsid monomers derived from different library members. Here, we investigate the prevalence of cross-packaging and mosaicism in simplified, minimal libraries using novel assays designed to assess capsid composition and packaging fidelity. We show that AAV library variants are prone to cross-packaging and capsid mosaic formation when produced at high plasmid levels, although to a lesser extent than in a recombinant context. We also provide experimental evidence that dilution of input library DNA significantly increases capsid monomer homogeneity and increases capsid:genome correlation in AAV libraries. Lastly, we determine that similar dilution methods yield higher-quality libraries when used for

Indexed as

aavadeno-associated virusbarcodecapsidcapsid mosaicscross-packaginglibrarymosaicviral genome

Identifiers

PMID31909084
PMCPMC6938944
OpenAlexW2989766830

What OpenQuestion 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 OpenQuestion graph.