An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus

Domenico Maione, Carlo Della Rocca, Patrizia Giannetti, Roberta D'Arrigo, Laura Liberatoscioli, Laura L. Franlin, Volker Sandig, Gennaro Ciliberto, Nicola La Monica, Rocco Savino

Research output: Contribution to journalArticlepeer-review

Abstract

Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained also in the presence of a preexisting immunity to adenovirus, a condition found in a high proportion of the adult human population. In this study we performed intramuscular delivery of helper-dependent vectors carrying mouse erythropoietin as a marker transgene. We found that low doses of helper-dependent adenoviral vectors can direct long-lasting gene expression in the muscles of fully immunocompetent mice. The best performance - i.e., 100% of treated animals showing sustained expression after 4 months - was achieved with the latest generation helper-dependent backbones, which replicate and package at high efficiency during vector propagation. Moreover, efficient and prolonged transgene expression after intramuscular injection was observed with limited vector load also in animals previously immunized against the same adenovirus serotype. These data suggest that human gene therapy by intramuscular delivery of helper-dependent adenoviral vectors is feasible.

Original languageEnglish
Pages (from-to)5986-5991
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number11
DOIs
Publication statusPublished - May 22 2001

ASJC Scopus subject areas

  • Genetics
  • General

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