Evidence map›Paper›PMID 27069949›Full record

ArticleMolecular therapy. Methods & clinical development2016

Distribution of AAV8 particles in cell lysates and culture media changes with time and is dependent on the recombinant vector.

Bryan A Piras, Jason E Drury, Christopher L Morton, Yunyu Spence, Timothy D Lockey, Amit C Nathwani, Andrew M Davidoff, Michael M Meagher

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 26 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Bryan A PirasDepartment of Therapeutics Production & Quality, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Jason E DruryDepartment of Therapeutics Production & Quality, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Christopher L MortonDepartment of Surgery, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Yunyu SpenceDepartment of Surgery, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Timothy D LockeyDepartment of Therapeutics Production & Quality, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Amit C NathwaniUCL Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital , London, UK.
Andrew M DavidoffDepartment of Surgery, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
Michael M MeagherDepartment of Therapeutics Production & Quality, St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
St. Jude Children's Research Hospital · USUniversity College London · GB

Funding

Medical Research Council G0502121Medical Research Council G0902219Medical Research Council MR/L013185/1
6 · The paper itself

Abstract

With clinical trials ongoing, efficient clinical production of adeno-associated virus (AAV) to treat large numbers of patients remains a challenge. We compared distribution of AAV8 packaged with Factor VIII (FVIII) in cell culture media and lysates on days 3, 5, 6, and 7 post-transfection and found increasing viral production through day 6, with the proportion of viral particles in the media increasing from 76% at day 3 to 94% by day 7. Compared to FVIII, AAV8 packaged with Factor IX and Protective Protein/Cathepsin A vectors demonstrated a greater shift from lysate towards media from day 3 to 6, implying that particle distribution is dependent on recombinant vector. Larger-scale productions showed that the ratio of full-to-empty AAV particles is similar in media and lysate, and that AAV harvested on day 6 post-transfection provides equivalent function in mice compared to AAV harvested on day 3. This demonstrates that AAV8 production can be optimized by prolonging the duration of culture post-transfection, and simplified by allowing harvest of media only, with disposal of cells that contain 10% or less of total vector yield. Additionally, the difference in particle distribution with different expression cassettes implies a recombinant vector-dependent processing mechanism which should be taken into account during process development.

Identifiers

PMID27069949
PMCPMC4813606
OpenAlexW2328143383

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.