The introduction of functional genes into cells offers a new pharmaceutical approach to treat various human diseases. Vical has developed proprietary technology for the intracellular delivery of DNA based on the presentation of DNA or DNA-lipid complexes to animal tissues or cultured cells. Although lipid-independent transfection with DNA can be accomplished in a small number of myocytes when DNA is directly injected into heart or skeletal muscle tissue, the transfection of all other tissues and of all cultured cells virtually requires that the DNA be first complexed with cationic lipid or some other delivery vector. During SBIR Phase I period, Vical developed a quantitative microplate bioassay to measure reporter DNA transfection efficiencies in vitro. Vical employed this assay to quantify transfection potencies of various cationic lipid preparations and, synthesized two novel lipid preparations that possessed much higher transfection activity than any currently available cationic lipids. During this SBIR Phase II period, Vical proposes to synthesize at least 16 additional cationic lipids in two homologous series, and to determine structure/activity relationships based on in vitro (tissue culture) and in vivo assays. Each lipid preparation will be tested for in vitro and in vivo transfection efficiencies relative to existing lipids and relative to one another. Active lipids will be further tested for activity under different transfection conditions and for intrinsic toxicity. Dose limiting systemic toxicity of selected compounds will be determined by a contract laboratory, under GLP conditions. Completion of these studies will position this technology for Phase III sponsorship by a corporate partner interested in developing applications for pharmaceutical use.
