Malariologist Robert Barker of Hybridon Inc. and Hybridon'sscientific founder, molecular biologist Paul Zamecnik, report usingantisense molecules to cripple the growth of Plasmodium falciparumin vitro. (See a related story on p. 1.)
Their paper, titled "Inhibition of Plasmodium falciparum malariausing antisense oligonucleotides," appears in the current Proceedingsof the National Academy of Sciences (PNAS), dated Jan. 9, 1996.
Zamecnik, the article's senior author, told BioWorld Today, "Wetargeted the antisense oligos against the parasite's dihydrofolatereductase thymidylate synthase gene, [which mediates folic-acidsynthesis and DNA replication]. This inhibited replication of theorganism in tissue-cultured red blood cells.
"If you block thymidine formation," Zamecnik explained, "then youstall the parasite's ability to form its plasmodia. It works just as wellin drug-resistant P. falciparum as in drug-sensitive ones," he added.
He and Barker are almost ready to put their construct "into a mouseor baby-chick model, and try the same thing on them."
Known to many as "the father of antisense," Zamecnik is now asenior scientist at the Worcester Foundation for BiomedicalResearch, in Shrewsbury, Mass., and chairman of Worcester-basedHybridon's scientific advisory committee. He described hiscollaborator, Barker, as "a card-carrying tropical medicine man,"seconded from Hybridon's staff to work with him on this project inthe Foundation's laboratory.
"I provided the targeting and background for using antisense."Zamecnik concluded. "It's our thought that maybe we can blockdrug-resistant malaria." _ David N. Leff
(c) 1997 American Health Consultants. All rights reserved.