There are an estimated 100,000 genes in the human genome. Novel techniques of gene mapping and sequencing are giving the clinician access to a constantly growing pool of genetic material for possible use in human genetic therapy. The present state of the art in gene delivery systems is however sadly lacking efficiency. The cationic lipids breakthrough of 1987 has not kept up to former expectations, there is even a serious concern about their practicality, mainly because of their cytotoxic properties that precludes their safe administration in humans. The concept of using polyfluorinated 1,2-diacylglyceryl esters of trigonelline is a novel approach in the design of cationic lipids. Their readily biodegradable structure is prone to biotransformations by ubiquitous tissue and plasma esterases to a polyfluorinated diacyl glycerol and trigonelline. Polyfluorinated diacylglyceryl structures are known for their lack of hemolytic properties, and trigonelline is a naturally occurring and innocuous substance. The new cationic lipids are therefore expected to be innocuous. When complexed with polynucleotides, the fluorinated cationic lipids are expected to serve the dual purpose of gene masking and of delivery of genetic payload across the cellular membrane. Because of the short half-life of the novel cationic lipids and the innocuous properties of their metabolites, cytotoxicity and hemolysis usually observed with present state of the art cationic lipids will be avoided. As a result, the F-lipids are expected to be useful in gene delivery systems for administration in humans.Proposed commercial application:Due to the gene masking and charge neutralization properties of the object of the invention, there is excellent opportunity for commercial application in gene delivery systems for human therapy.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
