The present invention provides novel phosphonic acid-based cationic lipids of the general structure: ##STR1## or a salt, or solvate, or enantiomers thereof wherein; (a) R.sub.1 is a lipophilic moiety; (b) R.sub.2 is a positively charged moiety; (c) R.sub.3 is a lipophilic moiety of 1 to about 24 carbon atoms, a positively charged moiety, or a negatively charged moiety; (d) n is an integer from 0 to 8; (e) X.sup.- is an anion or polyanion; (f) Y is N or O, and (g) m is an integer from 0 to a number equivalent to the positive charge(s) present on the lipid.The present invention further provides compositions of these lipids with polyanionic macromolecules, methods for interfering with protein expression in a cell utilizing these compositions and a kit for preparing the same.