Paramyxoviruses comprising modified transcription start...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/86 (2006.01) A61K 31/7105 (2006.01) A61K 48/00 (2006.01) C07K 14/115 (2006.01) C12N 15/45 (2006.01)

Patent

CA 2376106

Virus vectors of the family Paramyxoviridae in which the transcription initiation sequence has been modified and thus the expression of genes located downstream thereof has been modified; a process for producing the same; and use of the same. By measuring the transcription initiation efficiency of each gene carried by Sendai viruses, it is clarified that the transcription initiation sequence of F gene has a significantly lower ability to promote the transcription than the three other transcription initiation sequences. When the transcription initiation sequence of the F gene of wild type Sendai virus is substituted by the transcription initiation sequence of the P/M/HN genotype showing a high efficiency, the F gene of the resultant Sendai virus mutant and genes located downstream thereof show elevated expression doses. It is also found out that this mutant proliferates more quickly than the wild type. The above-described vectors are useful in producing medicinal compositions and vaccines.

Cette invention, qui a trait à des vecteurs viraux de la famille des Paramoxyviridae chez qui la séquence d'initiation de transcription a été modifiée, ce qui a eu pour effet de modifier également l'expression des gènes situés en aval de cette séquence, concerne également l'utilisation qui est faite de ces vecteurs. L'évaluation de l'efficacité de l'initiation de la transcription de chaque gène porté par des virus Sendai, démontre que la séquence d'initiation de transcription du gène F est bien moins apte à déclencher la transcription que les trois autres séquences d'initiation de transcription. Lorsque la séquence d'initiation de transcription du gène F du virus Sendai de type sauvage est remplacée par la séquence d'initiation de transcription du génotype P/M/HN faisant montre d'une grande efficacité, le gène F du virus Sendai résultant mutant et les gènes se trouvant en aval montrent des doses élevées d'expression. Il a également été découvert que ce mutant prolifère plus rapidement que le type sauvage. Les vecteurs susmentionnés se révèlent des plus utiles en matière de production de composition médicinales et de vaccins.

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