Adenovirus serotype 34 vectors, nucleic acids and virus...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/861 (2006.01) A61K 39/21 (2006.01) A61K 48/00 (2006.01) A61P 31/18 (2006.01) C12N 5/10 (2006.01) C12N 7/01 (2006.01) C12N 15/00 (2006.01) C12N 15/01 (2006.01) C12N 15/33 (2006.01)

Patent

CA 2519207

Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g, fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication- defective adenovirus of serotype 34, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for the delivery and expression of exogenous genes are provided.

Les sérotypes adénoviraux diffèrent par leur tropisme naturel. Il a été découvert que les divers sérotypes de l'adénovirus sont différents au moins du fait de leurs protéines capsides (p. ex. des protéines de base penton et des protéines hexon), lesquelles protéines sont responsables de la liaison cellulaire (protéines fibreuses) et participent à la réplication de l'adénovirus. Cette différence des sérotypes due au tropisme et aux protéines capsides est à l'origine des nombreux efforts de recherche visant à réorienter le tropisme de l'adénovirus par modification des protéines capsides. La méthode de l'invention contourne les exigences de modification des protéines capsides dans la mesure où elle présente un adénovirus recombinant dépourvu de réplication du sérotype 34, un sérotype adénoviral rare. L'invention concerne en outre des méthodes de génération de l'adénovirus recombinant de remplacement, et un moyen de mise en oeuvre de l'adénovirus recombinant pour le transfert et l'expression de gènes exogènes.

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