MUTANT DEOXYADENOSINE KINASE ENZYMES AND THEIR USE

摘要

The application relates to the field of suicide gene therapy using expression vectors encoding a deoxynucleotide kinase capable of converting prodrugs into cytotoxic drugs. Mutated chicken deoxyadenosine kinase polypeptides and nucleotides encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides for the treatment of malignancies and viral infections, methods of sensitising cells to prodrugs, and methods of inhibiting pathogenic agents in warm-blooded animals using said mutated dAKs. This invention relates to newly created mutated polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. In particular the mutated polynucleotide when compared to the non-mutated polynucleotide and when expressed in a bacterial or eukaryotic cell decreases the LD₁₀₀ of AraG. More particularly, the mutated polypeptides of the present invention are chicken (Gallus gallus) deoxyadenosinekinases. The invention also relates to medical use of such polypeptides.