Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovims vectors

Sandeep K. Tripathy, Hugh B Black, Eugene Goldwasser, Jeffrey M. Leiden

Research output: Contribution to journalArticle

597 Citations (Scopus)

Abstract

The use of replication-defective adenoviruses (RDAd) for human gene therapy has been limited by host immune responses that result in transient recombinant gene expression in vivo. It remained unclear whether these immune responses were directed predominantly against viral proteins or, alternatively, against foreign transgene-encoded proteins. In this report, we have compared the stability of recombinant gene expression in adult immunocompetent mice following intramuscular (i.m.) injection with identical RDAd encoding self (murine) or foreign (human) erythropoietin. Our results demonstrate that immune responses directed against foreign transgene-encoded proteins are the major determinants of the stability of gene expression following i.m. injection of RDAd. Moreover, we demonstrate long-term recombinant gene expression in immunocompetent animals following a single i.m. injection of RDAd encoding a self protein. These findings are important for the design of future preclinical and clinical gene therapy trials.

Original languageEnglish (US)
Pages (from-to)545-550
Number of pages6
JournalNature Medicine
Volume2
Issue number5
StatePublished - 1996
Externally publishedYes

Fingerprint

Protein Stability
Transgenes
Gene expression
Intramuscular Injections
Adenoviridae
Gene Expression
Gene therapy
Injections
Genetic Therapy
Proteins
Human Adenoviruses
Viral Proteins
Erythropoietin
Animals

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovims vectors. / Tripathy, Sandeep K.; Black, Hugh B; Goldwasser, Eugene; Leiden, Jeffrey M.

In: Nature Medicine, Vol. 2, No. 5, 1996, p. 545-550.

Research output: Contribution to journalArticle

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