Future of adenoviruses in the gene therapy of arthritis

Christopher H. Evans, Steven C. Ghivizzani, Thomas A. Oligino, Paul D. Robbins

Research output: Contribution to journalComment/debate

31 Scopus citations

Abstract

Recombinant adenoviruses are straightforward to produce at high titres, have a promiscuous hostrange, and, because of their ability to infect nondividing cells, lend themselves to in vivo gene delivery. Such advantages have led to their widespread and successful use in preclinical studies of arthritis gene therapy. While adenoviral vectors are well suited to 'proof of principle' experiments in laboratory animals, there are several barriers to their use in human studies at this time. Transient transgene expression limits their application to strategies, such as synovial ablation, which do not require extended periods of gene expression. Moreover, there are strong immunological barriers to repeat dosing. In addition, safety concerns predicate local, rather than systemic, delivery of the virus. Continued engineering of the adenoviral genome is producing vectors with improved properties, which may eventually overcome these issues. Promising avenues include the development of 'gutted' vectors encoding no endogenous viral genes and of adenovirus-AAV chimeras. Whether these will offer advantages over existing vectors, which may already provide safe, long-term gene expression following in vivo delivery, remains to be seen.

Original languageEnglish (US)
Pages (from-to)142-146
Number of pages5
JournalArthritis Research
Volume3
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Gene expression
  • Gene therapy
  • Immunity
  • Vector
  • Virus

ASJC Scopus subject areas

  • Rheumatology

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    Evans, C. H., Ghivizzani, S. C., Oligino, T. A., & Robbins, P. D. (2001). Future of adenoviruses in the gene therapy of arthritis. Arthritis Research, 3(3), 142-146. https://doi.org/10.1186/ar291