Targeted adenovirus vectors for delivery of heterologous genes

US6911199B2 · kind B2 · utility

Assignee

• AVENTIS PHARMA S.A. · FR

Inventors

• Emmanuelle Vigne · L'Haÿ-les-Roses, FR
• Jean-Francois Dedieu · Paris, FR
• Martine Latta · Charenton-le-Pont, FR
• Patrice Yeh · Paris, FR
• Michel Perricaudet · Rambouillet, FR

Key dates

• Filing date: Feb 22, 2001
• Grant date: Jun 28, 2005
• Expiry date: Mar 1, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2810/857
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.