Vectors and methods for immunization or therapeutic protocols

A - Human Necessities – 61 – K

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A61K 35/00 (2006.01) A61K 39/29 (2006.01) A61K 39/39 (2006.01) A61K 48/00 (2006.01) C12N 15/63 (2006.01) C12N 15/861 (2006.01)

Patent

CA 2301575

The present invention shows that DNA vaccine vectors can be improved by removal of CpG-N motifs and optional addition of CpG-S motifs. In addition, for high and long-lasting levels of expression, the optimized vector should include a promoter/enhancer that is not down-regulated by the cytokines induced by the immunostimulatory CpG motifs. Vectors and methods of use for immunostimulation are provided herein. The invention also provides improved gene therapy vectors by determining the CpG-N and CpG-S motifs present in the construct, removing stimulatory CpG (CpG-S) motifs and/or inserting neutralizing CpG (CpG-N) motifs, thereby producing a nucleic acid construct providing enhanced expression of the therapeutic polypeptide. Methods of use for such vectors are also included herein.

La présente invention concerne l'amélioration des vecteurs de vaccin d'ADN par élimination de motifs CpG-N et addition éventuelle de motifs CpG-S. En outre, dans le cas de niveaux d'expression élevés et durables, le vecteur optimisé inclut un promoteur/renforçateur qui n'est pas rétro-régulé par les cytokines induites par les motifs CpG immunostimulateurs. L'invention concerne également des vecteurs et des procédés d'immunostimulation. L'invention concerne, en outre, l'amélioration des vecteurs de thérapie génique consistant à déterminer les motifs CpG-N et CpG-S présents dans le produit de recombinaison, à éliminer des motifs stimulateurs CpG(CpG-S) et/ou à insérer des motifs neutralisant CpG(CpG-N), de façon à obtenir un produit de recombinaison d'acide nucléique assurant une expression améliorée du polypeptide thérapeutique. L'invention concerne des procédés de fabrication des vecteurs précités.

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