Compositions of and methods for using synthetic retinal derivatives as retinoid replacements and opsin agonists are provided.

Disclosed are cationic lipids comprising a vitamin substructure and an ionizable nitrogen-containing group. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Disclosed are cationic lipids comprising a vitamin substructure and an ionizable nitrogen-containing group. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Compositions of and methods for using synthetic retinal derivatives as retinoid replacements and opsin agonists are provided.

Esters of O-substituted hydroxy carboxylic acids are provided having Formula 1, or 2, or both Formulas 1 and 2: ##STR00001##
wherein R and R.sup.1 are independently selected from the group consisting of substituted and unsubstituted, branched- and straight-chain, saturated, unsaturated, and polyunsaturated C.sub.1-C.sub.22 alkyl, substituted and unsubstituted C.sub.3-C.sub.8 cycloalkyl, substituted and unsubstituted C.sub.6-C.sub.20 carbocyclic aryl, and substituted and unsubstituted C.sub.4-C.sub.20 heterocyclic; wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen; and wherein n is 1-6. Process of producing esters of O-substituted hydroxy carboxylic acids are also provided.

Esters of O-substituted hydroxy carboxylic acids are provided having Formula 1, or 2, or both Formulas 1 and 2: ##STR00001##
wherein R and R.sup.1 are independently selected from the group consisting of substituted and unsubstituted, branched- and straight-chain, saturated, unsaturated, and polyunsaturated C.sub.1-C.sub.22 alkyl, substituted and unsubstituted C.sub.3-C.sub.8 cycloalkyl, substituted and unsubstituted C.sub.6-C.sub.20 carbocyclic aryl, and substituted and unsubstituted C.sub.4-C.sub.20 heterocyclic; wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen; and wherein n is 1-6. Process of producing esters of O-substituted hydroxy carboxylic acids are also provided.

A nanosized complex includes a nucleic acid and a compound comprising formula (I):

##STR00001## wherein R.sup.1 is an alkylamino group or a group containing at least one aromatic group; R.sup.2 and R.sup.3 are independently an aliphatic group or hydrophobic group; R.sup.4 and R.sup.5 are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, or an aromatic group, or a polymer, a targeting group, a detectable moiety, or a linker, or a combination thereof, and at least one of R.sup.4 and R.sup.5 includes a retinoid or retinoid derivative that targets and/or binds to an interphotoreceptor retinoid binding protein; a, b, c, and d are independently an integer from 1 to 10; and pharmaceutically acceptable salts thereof.

A nanosized complex includes a nucleic acid and a compound comprising formula (I):

##STR00001## wherein R.sup.1 is an alkylamino group or a group containing at least one aromatic group; R.sup.2 and R.sup.3 are independently an aliphatic group or hydrophobic group; R.sup.4 and R.sup.5 are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, or an aromatic group, or a polymer, a targeting group, a detectable moiety, or a linker, or a combination thereof, and at least one of R.sup.4 and R.sup.5 includes a retinoid or retinoid derivative that targets and/or binds to an interphotoreceptor retinoid binding protein; a, b, c, and d are independently an integer from 1 to 10; and pharmaceutically acceptable salts thereof.

Disclosed are cationic lipids comprising a vitamin substructure and an ionizable nitrogen-containing group. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Disclosed are cationic lipids comprising a vitamin substructure and an ionizable nitrogen-containing group. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.