POLYCATIONIC METHYL PHOSPHOLIPIDS FOR IMPROVED DELIVERY OF NUCLEIC ACIDS TO EUKARYOTIC CELLS

1 - 40 . (canceled)

41 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

each X independently is selected from —O—, —OC(O)O—, —C(O)O—, and —O(O)C—, -;

Y is independently (C 1 -C 6 )alkyl;

each R is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, wherein each R group is optionally independently substituted by 1-3 substituent groups, each substituent group independently selected from amino, hydroxyl, (CH 2 ) j OR 11 , (CH 2 ) j C(O)R 11 , (CH 2 ) j C(O)OR 11 , (CH 2 ) j OC(O)R 11 , (CH 2 ) j NR 12 R 13 , (CH 2 ) j C(O)NR 12 R 13 , (CH 2 ) j OC(O)NR 12 R 13 , (CH 2 ) j N 14 RC(O)R 11 , (CH 2 ) j N 14 RC(O)OR 11 , (CH 2 ) j N 14 RC(O)NR 12 R 13 , and (CH 2 ) j N 14 RC(NH)NR 12 R 13 , wherein each j is independently an integer selected from 0 to 6;

R 1 is independently selected from alkyl and (CH 2 ) j OR 11 ;

R 3 is independently selected from H and —(CH 2 ) j NR 12 R 13 ; and

R 11 , R 12 , R 13 , and R 14 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, perfluoroalkyl, and cycloalkyl, where the alkyl or alkenyl is optionally substituted with one or more substituent selected from the group consisting of amino, primary amino, secondary amino, hydroxy, alkoxy, and hydroxyalkyl.

42 . The compound of claim 41 , wherein:

each X independently is selected from —O—, —C(O)O—, and —O(O)C—;

Y is independently (C 1 -C 6 )alkyl;

each R is independently selected from substituted or unsubstituted (C 1 -C 20 )alkyl, substituted or unsubstituted (C 2 -C 20 )alkenyl, and substituted or unsubstituted (C 2 -C 20 )alkynyl;

R 1 is independently selected from (C 1 -C 6 )alkyl and (CH 2 ) j OR 11 ; and

R 3 is independently selected from H and —(CH 2 ) j NR 12 R 13 ;

R 11 is independently selected from hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, trifluoromethyl, and (C 3 -C 8 )cycloalkyl; and

R 12 , R 13 are each independently selected from alkyl, alkenyl, and alkynyl, where the alkyl or alkenyl is optionally substituted with one or more substituent selected from the group consisting of amino, primary amino, secondary amino, hydroxy, alkoxy, and hydroxyalkyl.

43 . The compound of claim 42 , wherein:

each X independently is selected from —C(O)O— and —O(O)C—;

Y is independently (C 1 -C 4 )alkyl;

each R is independently selected from (C 1 -C 20 )alkyl, (C 2 -C 20 )alkenyl, and (C 2 -C 20 )alkynyl;

R 1 is independently selected from (C 1 -C 6 )alkyl and (CH 2 ) j OR 11 ;

R 3 is —(CH 2 ) j NR 12 R 13 ;

R 11 is independently selected from hydrogen and (C 1 -C 6 )alkyl; and

R 12 , R 13 are each independently selected from alkyl and alkenyl, where the alkyl or alkenyl is optionally substituted with one or more substituent selected from the group consisting of amino, primary amino, secondary amino, hydroxy, alkoxy, and hydroxyalkyl.

44 . The compound of claims 43 , wherein:

each X independently is selected from —C(O)O— and —O(O)C—;

Y is independently —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 —;

each R is independently selected from (C 2 -C 20 )alkyl and (C 2 -C 20 )alkenyl;

R 1 is independently selected from —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 )CH 3 , —C(CH 3 ) 3 , and —CH 2 CH(OH)CH 2 (OH); and

R 3 is independently selected from —CH 2 NH 2 and —(CH 2 ) j NR 12 R 13 .

45 . The compound of claims 44 , wherein:

each X independently is selected from —C(O)O— and —O(O)C—;

Y is independently —CH 2 CH 2 ;

each R is independently selected from n-propyl, n-butyl, n-pentyl, n-hexyl, lauryl, myristyl, palmityl, stearyl, linoleyl, oleyl, palmitoleyl;

R 1 is independently selected from —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 )CH 3 , —C(CH 3 ) 3 and —CH 2 CH(OH)CH 2 (OH); and

R 3 is —(CH 2 ) j NR 12 R 13 ; and

R 12 and R 13 are each independently selected from, n-propyl, n-butyl, n-pentyl, isoamyl, n-hexyl, lauryl, myristyl, palmityl, stearyl, linoleyl, oleyl, palmitoleyl; and

wherein j is independently an integer selected from 0 to 6.

46 . A composition comprising a compound of Formula of claim 41 and at least one or more neutral lipids.

47 . A composition comprising a compound of Formula I of claim 41 , and at least one or more cationic lipids, and/or at least one or more neutral lipids.

48 . A composition comprising a compound of Formula I of claim 41 , and one or more polyamine transfection agents.

49 . A composition comprising a compound of Formula I of claim 41 , and one or more fusion agents.

50 . A composition comprising a compound of Formula I of claim 41 , and one or more cell surface ligands, wherein said one or more cell surface ligands optionally comprises a polycationic nucleic acid binding moiety.

51 . A composition comprising a compound of Formula I of claim 41 , and one or more nuclear localization peptides or one or more protein cell surface ligands, wherein said one or more nuclear localization peptides or said one or more protein cell surface ligands optionally comprises a polycationic nucleic acid binding moiety.

52 . A composition comprising a compound of Formula I of claim 41 , and one or more amphipathic peptides, wherein said one or more amphipathic peptide optionally is covalently linked to a polycationic nucleic binding moiety, and wherein said amphipathic peptide optionally functions as a fusion agent.

53 . A composition comprising a compound of Formula I of claim 41 , further comprising one or more nucleic acids.

54 . The composition of claim 53 , wherein the one or more nucleic acids are selected from DNA and RNA.

55 . The composition of claim 54 , wherein the RNA is an RNAi molecule.

56 . A method of introducing a nucleic acid, protein, or peptide into a eukaryotic cell, comprising contacting the cell with a composition according to claim 53 .

57 . The method of claim 56 , wherein the cell is a human cell.

58 . The method of claim 56 , wherein the cell is an animal cell.

59 . A method of expressing a protein in a cell, comprising contacting the cell with an expression vector encoding the protein and a compound of Formula I of claim 41 .

60 . A method of inhibiting expression of a protein in a cell, comprising contacting the cell with an RNAi molecule and a compound of Formula I of claim 41 .