ABSTRACT

Cationic liposomes have the capacity to mediate the entry of associated nucleic acids into the cytoplasm by a poorly understood process involving perturbation of the plasma membrane and/or the membrane of endocytic vesicles. Liposomes used for the purpose of transport of nucleotides may encapsulate the agents or bind them on their surfaces. The capacity of antisense oligonucleotides to distinguish normal and mutated Ras oncogenes, the sequences of which differ by a single nucleotide. The difference between DNA intercalating drugs, which have little or no sequence specificity, and the selective inhibition of particular genes or the mRNAs they encode corresponds to a fundamental change and reveals new perspectives in pharmacology. The drug development requires that appropriate inhibitors be found by screening or by modeling, which are inefficient and expensive, and which can yield molecules which, even if good enzyme inhibitors, may have poor solubility or bioavailability.