Lipid-based systems for the intracellular delivery of genetic drugs

Currently available delivery systems for genetic drugs have limited utility for systemic applications. Cationic liposome/plasmid DNA or oligonucleotid e complexes are rapidly cleared from circulation, and the highest levels of activity are observed in 'first pass' organs, such as the lungs, spleen an d liver. Engineered viruses can generate an immune response, which compromi ses transfection resulting from subsequent injections and lack target speci ficity. A carrier, which can accumulate at sites of diseases such as infect ions, inflammations and tumours, has to be a small, neutral and highly seru m-stable particle, which is not readily recognized by the fixed and free ma crophages of the reticuloendothelial system (RES). This review summarizes l ipid-based technologies for the delivery of nucleic acid-based drugs and in troduces a new class of carrier systems, which solve, at least in part, the conflicting demands of circulation longevity and intracellular delivery. P lasmid DNA and oligonucleotides are entrapped into lipid particles that con tain small amounts of a positively charged lipid and are stabilized by the presence of a polyethylene glycol (PEG) coating. These carriers protect nuc leic acid-based drugs from degradation by nucleases, are on average 70 nm i n diameter, achieve long circulation lifetimes and are capable of transfect ing cells.