Injection of a naked gene construct based on a section of theAIDS virus has induced both an antibody response andactivation of killer T cells in mice, scientists from Vical Inc.were to report today at an AIDS conference in San Diego.

However, the particular plasmid, which was developed byChiron Corp., was only used to validate Vical's technology, andVical does not intend to develop it as an AIDS therapeutic,company officers told BioWorld.

The results do show that injections into muscle of a plasmidvector containing HIV gene sequences could provide a route toAIDS vaccines and immunotherapies. Killer T cells generatedby the treatment "are not commonly shown" with other AIDSstrategies tested so far, said Dannie King, Vical president andchief executive, "especially at the levels we have seen."

In a separate report last week, Duke University medical centerresearchers said they have also induced killer T cells. Thescientists, writing in the current issue of the Proceedings ofthe National Academy of Sciences, vaccinated mice withsynthetic hybrid peptides that incorporate regions of the HIVgp120 V3 and gp41 coat proteins.

The Vical results add to demonstrations that DNA or RNA genesequences can be directly injected into animals withtherapeutic effect, without having to use a virus as a ferry toget the gene into the host's genome.

In June, Merck & Co. Inc. signed a licensing agreement withVical to use the privately held San Diego company's approachto develop vaccines. Vical also has an independent project todevelop therapeutics based on its naked gene approach,targeting the viruses that cause AIDS, hepatitis B and herpes.

Vical's technology, developed with the University ofWisconsin, injects naked DNA or RNA from an infective agentinto a muscle. The gene product is indeed secreted by theinjected animal, experiments show, and the animal's systemwill respond by making cytotoxic T cells that will then kill anycells that are infected and display the antigen.

For some reason, muscle tissue can take up and read out thenaked, foreign genetic material. "We have a crew of peopletrying to sort out why muscle is unique," King told BioWorld. --Roberta Friedman, Ph.D.

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