Inhibition of Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase mRNA by antisense oligodeoxynucleotide sequence

Comparative biochemical studies between the malaria parasite, Plasmodium falciparum, and its host have revealed differences in a number of metabolic pathways. For example, the parasite has enzymes to carry out de novo pyrimidine synthesis but is not capable of de novo synthesis of purine nucleotides. The parasite must salvage purines from its host to supply the requirement for purine nucleotides. The enzyme required for this salvage is hypoxanthine-guanine phosphoribosyltransferase This enzyme has been suggested as a target for chemotherapy by the design of analogue substrate inhibitors of the parasite enzyme. An alternate strategy, and one which we have been exploring, is the inhibition of expression of the parasite HPRT using antisense oligodeoxynucleotides