Adenovirus vectors for gene therapy

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/86 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C12N 15/12 (2006.01) C12N 15/861 (2006.01)

Patent

CA 2161962

The present invention comprises an improved adenovirus vector and methods for making and using such vectors. The adenovirus vectors of the present invention retain at least a portion of the adenoviral E3 region, carry a deletion of at least a portion of the adenoviral E1 region. Vectors of the present invention preferably also include an additional deletion to accommodate a transgene and/or other mutations which result in reduced expression or over-expression of adenoviral protein and/or reduced viral replication. The vectors of the present invention further include a transgene operatively-linked thereto. By reducing or eliminating viral replication and viral protein expression, the immune response of the infected host to the virus and viral protein is decreased and persistance of transgene expression can be increased. The adenovirus vectors of the present invention are thus particularly useful in gene transfer and therapy.

L'invention concerne des vecteurs d'adénovirus améliorés ainsi que des procédés de fabrication de ces derniers. Les vecteurs d'adénovirus selon l'invention retiennent au moins une partie de la région adénovirale E3, et présentent une délétion d'au moins une partie de la région adénovirale E1. Ces vecteurs comprennent également, de préférence, une délétion supplémentaire permettant à ces derniers de recevoir un transgène et/ou d'autres mutations induisant l'expression réduite ou la surexpression de protéine adénovirale et/ou une replication virale réduite. Les vecteurs selon l'invention comprennent également un transgène lié à ces derniers de manière active. En réduisant ou en éliminant la réplication virale et l'expression protéique virale, on réduit la réponse immunitaire de l'hôte infecté au virus et à la protéine virale, et on peut augmenter la persistance de l'expression transgénique. Les vecteurs d'adénovirus selon l'invention sont, ainsi, particulièrement utiles dans le transfert et la thérapie géniques.

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