MALARIA MEROZOITE SURFACE PROTEIN ANTISENSE OLIGODEOXYNUCLEOTIDES LACK ANTISENSE ACTIVITY BUT FUNCTION AS POLYANIONS TO INHIBIT RED-CELL INVASION

The effects on malaria parasite growth of antisense and sense oligodeo xynucleoside phosphorothioates based on a merozoite surface protein mR NA was examined. Specific antisense effects of the oligonucleotides co uld not be demonstrated over three cycles of schizogony or when added as a complex with cationic liposomes. Antisense and sense oligonucleot ides however, inhibit merozoite invasion of red blood cells at similar concentrations to dextran sulphate, a polyanion, as determined by mic roscopy and [H-3]hypoxanthine incorporation into DNA. Neutralisation o f the negative charge on the oligonucleotides by binding to cationic l ipid liposomes, prevented the inhibition of merozoite invasion. We pos tulate that oligonucleotides because of their polyanionic nature inter fere with the binding of merozoites to receptors on red blood cells an d that polyanions may be useful in malaria therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.