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Protease-deleted adenovirus as an alternative for replication-competent adenovirus vector

From National Research Council Canada

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DOIResolve DOI: https://doi.org/10.1016/j.virol.2023.07.009
AuthorSearch for: 1ORCID identifier: https://orcid.org/0000-0003-2040-5665; Search for: 1; Search for: 1ORCID identifier: https://orcid.org/0000-0002-8265-2111
Affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FunderSearch for: National Research Council Canada
FormatText, Article
Subjectprotease-deleted adenovirus; single-cycle adenovirus vector; replication-competent adenovirus vector; replication-defective adenovirus; adenovirus E4 region
Abstract
For cancer therapy and vaccination an amplified expression of the therapeutic gene is desired. Previously, we have developed a single-cycle adenovirus vector (SC-AdV) by deleting the adenovirus protease (PS) gene. In order to keep the E1 region intact within the PS-deleted adenoviruses, we examined the insertion of two transgenes under the control of a constitutive or inducible promoters. These were inserted between E4 and the right inverted terminal repeat in a wide variety of backbones with various combinations of PS, E3 and E4 deletion. Our data showed that PS-deleted adenoviruses, expressed transgenes as strongly as replication-competent AdVs in HEK293A and a variant of HeLa cells. In a head-to-head comparison in four human cell lines, we demonstrated that SC-AdV, was comparable for transgene expression efficacy with its replication-competent counterpart. However, the SC-AdV expresses its transgene 10 to 16,000 times higher than its replication-defective counterpart.
Publication date
PublisherElsevier
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  • Virology 586, no. C (September 2023): 67–75.
LanguageEnglish
Peer reviewedYes
IdentifierS0042682223001484
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Record identifier32ca8bb2-9ad9-421a-8689-8516f1fbef7c
Record created2024-10-28
Record modified2024-10-28
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