Aventis Pharma S.a.

Rhone-poulenc Rorer S.a.

Emmanuelle Vigne

Michel Perricaudet

Patrice Yeh

Martine Latta

Patrice Denefle

C&eacute;cile Orsini

Edouard Prost

Jacques Mallet

Patrick Benoit

Fr&eacute;d&eacute;ric Revah

Joel Crouzet

Jo&euml;l Crouzet

Jean-Jacques Robert

Marc Abitbol

Hedi Mohamed Haddada

Jean-Francedillaois Dedieu

Cecile Orsini

Paul Roustan

H&eacute;l&egrave;ne Leblois-Prehaud

Bernard Klonjkowski

Laurent Naudin

Cécile Orsini

Philippe Horellou

Sandrine Seguret

Jean-Francois Dedieu

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

The present invention concerns defective recombinant adenoviruses containing an inserted gene encoding apolipoproteins, pharmaceutical compositions comprising the adenovirus, and their use for the treatment or prevention of pathologies linked to dyslipoproteinemias.

Recombinant adeno viruses comprising an inserted gene encoding apolipoprotein and their use in gene therapy for dyslipoproteinemias

Recombinant adenoviruses comprising a heterologous DNA sequence coding for basic blast growth factors (bFGF), preparation and uses thereof for the treatment and/or prevention of neurodegenerative diseases.

Recombinant adenoviruses coding for basic fibroblast growth factors (BFGF)

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

The invention concerns a method for reducing recombination phenomena among nucleic acids. It also concerns the use of said method for producing defective viruses not contaminated by replication particles. The invention further concerns novel viral constructs.

Adenovirus vectors and method for reducing homologous recombination phenomena

The invention concerns a method for producing recombinant virus. This method is based on the use of baculovirus for providing the complementary functions. It also concerns constructs used for implementing this method, the producing cells, and the resulting virus.

Method for producing recombinant virus

The present invention resides in use of a recombinant adenovirus of animal origin containing a heterologous DNA sequence for the preparation of a pharmaceutical composition intended for the therapeutic and/or surgical treatment of the human body.

Adenoviral vectors of canine origin

A novel method for preparing recombinant adenoviruses and the use of such adenoviruses in gene therapy are disclosed. Plasmids used in the construction of said adenoviruses are also disclosed.

Method for preparing a recombinant adenovirus genome

Recombinant adenoviruses comprising a heterologous DNA sequence coding for glial-derived neurotrophic growth factor (GDNF) are provided. The recombinant adenoviruses are useful in a method of expressing GDNF in a cell, wherein the cell is present in a mammal suffering from Parkinson's disease, comprising infecting said cell with a replication-defective recombinant adenovirus comprising a DNA sequence encoding GDNF operably linked to a promoter by administering the adenovirus into cells of the central nervous system. The recombinant adenoviruses of the invention are also useful in a method of treating Parkinson's disease comprising administering into cells of the central nervous system of a mammal suffering therefrom a replication defective recombinant adenovirus comprising ITRs, an encapsidation sequence and a DNA sequence encoding GDNF operably linked to a promoter, wherein the adenovirus E1 gene is non-functional and GDNF is expressed at a level that provides a therapeutic effect.

Recombinant adenoviruses coding for glial-derived neurotrophic factor (GDNF)

The present invention relates to new viral vectors derived from adenoviruses, their preparation and utilization in gene therapy. It relates particularly to defective recombinant adenoviruses wherein the Iva2 gene at least is inactivated.

Defective recombinant adenoviruses with inactivated IVa2 gene

Cells for the production of recombinant adenoviruses

Integrative recombinant adenoviruses, preparation thereof and

Recombinant adero viruses comprising an inserted gene encoding

Growing community of inventors

Ivry sur Seine, France

Emmanuelle Vigne