Transient expression of genes transferred in vivo into heart using first-generation adenoviral vectors: role of the immune response.

Abstract:

:Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transgene expression was maximal during the first week following injection, then declined and disappeared by day 21. An immunosuppressive treatment prolonged beta-Gal expression for at least 21 days. On the contrary, a preimmunization of the animals by two intraperitoneal injections of the vector led to a decreased transgene expression 48 hr after intramyocardial injection and to a barely detectable expression at the sixth day. Appearance of adenovirus neutralizing antibodies in preimmunized animals could have contributed to such a refractoriness to further adenoviral infection. Finally, a neonatal intrathymic injection of the vector was able to induce long-term LacZ expression for more than 2 months after heart injection, although neutralizing as well as anti-beta-Gal antibodies were detected in sera of the animals. These results indicate that an immune response against first-generation replication-defective adenoviral vectors is a major cause of transient transgene expression, a cellular response being most probably responsible for ablation of transgene expression in immunocompetent animals.

journal_name

Hum Gene Ther

journal_title

Human gene therapy

authors

Gilgenkrantz H,Duboc D,Juillard V,Couton D,Pavirani A,Guillet JG,Briand P,Kahn A

doi

10.1089/hum.1995.6.10-1265

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

1265-74

issue

10

eissn

1043-0342

issn

1557-7422

journal_volume

6

pub_type

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