Aventis Pharma S.a.

Rhone-poulenc Rorer S.a.

Martine Latta

Michel Perricaudet

Emmanuelle Vigne

Patrice Yeh

Edouard Prost

Patrice Denefle

C&eacute;cile Orsini

Cecile Orsini

Jean-Francedillaois Dedieu

Jean-Francois Dedieu

Cécile Orsini

A recombinant adenovirus in which the expression of a nucleic acid sequence coding for at least one homologous or heterologous gene of viral origin is placed under the control of an inducible promoter, is disclosed. The use of such recombinant adenoviruses for preparing AAVs, and a complementary cell line and preparation method therefor, are also disclosed. Furthermore, pharmaceutical compositions containing such an adenovirus are disclosed.

Recombinant adenoviruses, use thereof for preparing AAVS, complementary cell line, and pharmaceutical compositions containing said adenoviruses

Modification of internal sites of the adenovirus fiber protein and hexon protein permit effective targeting of adenovirus vectors. Accessible sites to redirect adenovirus targeting were identified. The HVR5 loop of the hexon protein and the HI loop of the fiber protein (knob) were highly permissive for the insertion of foreign protein sequences, which apparently did not impact on the viability and productivity of corresponding viruses. Accessibility and functionality of the epitope strongly depend on the size of the neighboring spacers. Other results suggest that short targeting peptides can be effectively fused to the C-terminus of the fiber protein. In a specific embodiment, a series of adenovirus vectors modified at the HVR5 site, the fiber protein HI loop, or the fiber protein C-terminus to target urokinase-type plasminogen activator receptor bearing cells were prepared. Such vectors are particularly useful for targeting the vasculature, e.g., for gene therapy of cancers or cardiovascular conditions.

Targeted adenovirus vectors for delivery of heterologous genes

Recombinant adenoviruses containing an inducible promoter controlling a gene of viral origin

Cells for the production of recombinant adenoviruses

Integrative recombinant adenoviruses, preparation thereof and

Growing community of inventors

Charenton le Pont, France

Martine Latta