Cyclosporin A does not affect adenoviral-mediated transgene expression of interleukin-2.

N. W. Wilkinson, David M Euhus

Research output: Contribution to journalArticle

Abstract

The adenoviral vector demonstrates efficient gene transfer and high transient gene expression making it an attractive vehicle for human gene therapy trials. Unfortunately, the virus stimulates a potent inflammatory immune response that limits transgene expression and makes repeat viral dosing ineffective. Transient immunosuppression has emerged as one technique to prolong adenoviral-mediated transgene expression and enable readministration of the viral vector. Cyclosporin A (CsA) causes immunosuppression by blocking the promotor/enhancer region of the gene for interleukin-2 (IL-2). The affect of CsA on transgene IL-2 expression was examined. Viral-mediated gene transfer was optimized in a human cell line using a type five adenoviral vector (Ad5) containing the gene for human IL-2 or bacterial beta-galactosidase (lac-Z) driven by a cytomegalovirus (CMV) promoter. CsA at various concentrations had no affect on IL-2 or lac-Z transgene expression. The immunosuppressive drug CsA is known to block native IL-2 transcription but has no affect on the adenoviral-mediated IL-2 or lac-Z transgene.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalInternational journal of surgical investigation
Volume2
Issue number6
StatePublished - 2001
Externally publishedYes

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Transgenes
Cyclosporine
Interleukin-2
Immunosuppression
Genes
Viral Genes
Immunosuppressive Agents
beta-Galactosidase
Cytomegalovirus
Genetic Promoter Regions
Genetic Therapy
Viruses
Gene Expression
Cell Line
Pharmaceutical Preparations

Cite this

Cyclosporin A does not affect adenoviral-mediated transgene expression of interleukin-2. / Wilkinson, N. W.; Euhus, David M.

In: International journal of surgical investigation, Vol. 2, No. 6, 2001, p. 491-498.

Research output: Contribution to journalArticle

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