Mutant purine nucleoside phosphorylase proteins and cellular...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/55 (2006.01) A61K 31/70 (2006.01) A61K 31/7088 (2006.01) A61K 48/00 (2006.01) C07H 19/16 (2006.01) C07H 21/04 (2006.01) C12N 1/20 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 7/01 (2006.01) C12N 9/10 (2006.01) C12N 9/12 (2006.01) C12N 9/24 (2006.01) C12N 15/00 (2006.01) C12N 15/54 (2006.01) C12N 15/63 (2006.01) C12N 15/86 (2006.01)

Patent

CA 2464349

A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumour cells and/or virally infected cells. A nucleotide sequence encoding mutant E. coli derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation withing target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upn enzymatic cleavage. A synthetic process for nucleosides is also detailed.

L'invention concerne une cellule hôte transformée ou transfectée de manière stable par un vecteur comprenant un séquence d'ADN codant pour des enzymes mutants de clivage des nucléosides puriques. Cette cellule hôte transformée ou transfectée peut être utilisée combinée à un substrat de purine, pour le traitement de cellules tumorales et/ou de cellules infectées par des virus. L'invention concerne également une séquence nucléotidique codant pour des protéines de purine nucléoside phosphorylase dérivées de E. coli qui, utilisées en combinaison avec un substrat approprié, permettent la production de toxines inhibant la croissance cellulaire anormale. L'invention concerne en outre un procédé permettant l'administration ciblée de toxines par génération de celles-ci dans des cellules cibles, ou par administration et transport de celles-ci dans les cellules à partir d'une source externe. L'invention concerne par ailleurs de nouveaux nucléosides puriques produisant une purine cytotoxique après clivage enzymatique, ainsi qu'un procédé de synthèse de nucléosides.

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