Evidence map›Paper›PMID 30440025›Full record

ArticlePloS one2018

Origins of truncated supplementary capsid proteins in rAAV8 vectors produced with the baculovirus system.

Lionel Galibert, Adrien Savy, Yohann Dickx, Delphine Bonnin, Bérangère Bertin, Isidore Mushimiyimana, Monique M van Oers, Otto-Wilhelm Merten

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 23 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 3 institutions in 3 countries.

Lionel GalibertGenethon, Evry, France.ORCID 0000-0002-2619-2464
Adrien SavyGenethon, Evry, France.ORCID 0000-0003-3663-9909
Yohann DickxGenethon, Evry, France.
Delphine BonninGenethon, Evry, France.
Bérangère BertinGenethon, Evry, France.
Isidore MushimiyimanaGenethon, Evry, France.
Monique M van OersWageningen University and Research, Laboratory of Virology, Wageningen, the Netherlands.
Otto-Wilhelm MertenGenethon, Evry, France.
Genethon (France) · FRUniversity of Eastern Finland · FIWageningen University & Research · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability to produce large quantities of recombinant Adeno-Associated Virus (rAAV) vectors is an important factor for the development of gene therapy-based medicine. The baculovirus/insect cell expression system is one of the major systems for large scale rAAV production. So far, most technological developments concerned the optimization of the AAV rep and cap genes in order to be expressed correctly in a heterologous system. However, the effect of the baculovirus infection on the production of rAAV has not been examined in detail. In this study we show that the baculoviral cathepsin (v-CATH) protease is active on several (but not all) rAAV serotypes, leading to a partial degradation of VP1/VP2 proteins. Subsequently, we identified the principal v-CATH cleavage site in the rAAV8 capsid proteins and demonstrated that the cleavage is highly specific. The proteolytic degradation of VP1/VP2 AAV capsid proteins reduces the infectivity of rAAV vectors but can be prevented by the use of a baculovirus vector with a deletion of the chiA/v-cath locus or by addition of the E64 protease inhibitor during production. Moreover, the codon optimization of AAV cap performed for several serotypes and originally aimed at the removal of potential alternative initiation codons, resulted in incorporation of additional forms of truncated VP1 into the rAAV capsids.

Indexed as

BaculoviridaeCapsidCapsid ProteinsCysteine EndopeptidasesDependovirusGenetic TherapyGenetic VectorsHumansCapsid ProteinsCysteine Endopeptidases

Identifiers

PMID30440025
PMCPMC6237368
OpenAlexW2901051898

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.