A protein aimed specifically at liver cells and armed with apayload of antisense DNA has inhibited hepatitis B virus fromattacking a culture of human liver cells, said TargeTech Inc.
The Meriden, Conn., company is a 3-year-old R&D spinoff of theUniversity of Connecticut Health Center.
The liver-seeking molecular "smart" missile consists of a cell-targeting glycoprotein that receptors on the liver cell surfacecan recognize and internalize and a poly-L-lysine linker thatbinds this "nose cone" to a single stranded DNA antisensesequence, complementary to key mRNA stretches of thehepatitis B viral genome.
TargeTech holds an exclusive worldwide license to theantisense DNA and liver-targeting technology from theuniversity.
George and Catherine Wu, who co-founded the company,carried out the in vitro virus-blocking experiment at theuniversity's department of medicine, where both areprofessors.
"Our strategy is to try to make an antisense sequence that, onceinside the cell, will free itself from the targeting and carriercomponents of the complex, and interact with all of the viralgenome's messenger RNA. This would not only shut downsurface antigens, but drastically diminish viral replication."
The results of the study, reported in the Journal of BiologicalChemistry, showed that receptor-bearing liver cellsaccumulated 12 times more antisense DNA after four hours'incubation with the complex than did controls exposed to free-floating antisense alone. The complex also reduced "all viralDNA forms in the medium by approximately 80 percent ...compared with antisense DNA alone."
Hepatologist T. Jake Liang of Massachusetts General Hospital,who is familiar with the Wus' work, told BioWorld, "The novelthing is targeted delivery of the antisense molecule to thespecific cell type. This is much more appealing than simplyputting the DNA into the bloodwtream, and to my knowledgehas not been done elsewhere."
Wu said he expects to move from petri dish to animal model"within the next two to three months." Samuel F. McKay,TargeTech's board chairman said that "clinical trials shouldbegin within a two-year period."
McKay said he expects the company to go public within thenext 24 months.
-- David Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.