A new way to get therapeutic genes into the body hassucceeded in lowering the cholesterol levels in rabbits withgenetically high levels of the fat.

The rabbit study by TargeTech Inc. demonstrated thecompany's strategy for getting genetic material, includingtherapeutic genes and antisense sequences, into the bodywithout relying on retroviruses.

In the research, George Wu, co-founder and scientific adviser,injected a plasmid expressing the human receptor forcholesterol, LDL, coupled to a molecule that targets the liver,into rabbits missing the blood LDL receptor. The genetreatment lowered the rabbits' cholesterol by 25 percent to 35percent for at least six days.

Safety concerns about the conventional retroviral approach hasforced researches to prove that their retroviral carriers arecompletely incapable of replicating once they have deliveredtheir therapeutic cargo.

But researchers still cannot predict where a retrovirallydelivered gene will end up. And gene therapies approved forhuman testing so far have had to include surgical removal oftissue and incubation in the laboratory to get the new genes toincorporate.

Vical Inc., another company whose approach to deliveringgenes avoids retroviruses,.has discovered that genes can beinjected directly into muscle. And at TargeTech, researcherssaid they will be able to get imported genes to transcribe insidemore than one of the body's tissues.

The liver is TargeTech's first target because the company'sfounders, gene delivery expert Catherine Wu and liver biologistGeorge Wu, knew that liver cells bear quick and efficientreceiver molecules for the sugar galactose. Linking geneconstructs to a negatively charged, galactose-bearing proteinwould get the genes specifically delivered into liver cells.

However, other organs can be targeted, using other carriersthat are taken up by other receptor systems, said GeorgeSpitalny, TargeTech vice president.

San Diego-based Vical plans to develop an AIDS vaccine andother therapeutics. TargeTech's first pipeline candidates aregenes and antisense molecules that could correct disordersarising in the liver, such as hepatitis, hemophilia, liver cancersand genetic emphysema, as well as high cholesterol.

TargeTech has filed for patents to "cover all" aspects of itsstrategy for ferrying DNA to whatever targets prove feasible,said Spitalny.

Founded in 1989, the privately held Meriden, Conn., companyhas completed a first round of financing with three partners:Connecticut Seed Ventures, 3i Ventures Corporations andVentures West. The company plans a new round of financingby early next year, said Samuel McKay, Connecticut SeedVentures' managing general partner and TargeTech's actingpresident and chief executive.

The Wus, who are on the faculty at the University ofConnecticut Health Center in Farmington, serve on thecompany's scientific advisory board.

-- Roberta Friedman, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.