NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

1 . A lipid having the structure

or a salt or isomer thereof,

wherein:

R 1 and R 2 are each independently for each occurrence optionally substituted C 10 -C 30 alkyl, optionally substituted C 10 -C 30 alkenyl, optionally substituted C 10 -C 30 alkynyl, or optionally substituted C 10 -C 30 acyl;

R 3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 2 -C 10 alkenyl, optionally substituted C 2 -C 10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol, optionally substituted mPEG, heteroaryl, or heterocycle;

E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O) 2 N(Q), S(O) 2 , N(Q)S(O) 2 , SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and,

Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalky, ω-phosphoalkyl or ω-thiophosphoalkyl.

2 . A lipid having the structure

or a salt or isomer thereof,

wherein,

E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O) 2 N(Q), S(O) 2 , N(Q)S(O) 2 , SS, O═N, aryl, heteroaryl, cyclic or heterocycle;

Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalky, ω-phosphoalkyl or ω-thiophosphoalkyl;

R 1 and R 2 and R x are each independently for each occurrence H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 10 -C 30 alkyl, optionally substituted C 10 -C 30 alkenyl, optionally substituted C 10 -C 30 alkynyl, or optionally substituted C 10 -C 30 acyl, provided that at least one of R 1 , R 2 and R x is not H;

R 3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 2 -C 10 alkenyl, optionally substituted C 2 -C 10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol, optionally substituted mPEG, heteroaryl, or heterocycle;

n is 0, 1, 2, or 3.

3 . A lipid particle comprising the lipid of claim 2 , or a salt or isomer thereof.

4 . A lipid particle comprising the lipid of claim 1 , or a salt or isomer thereof.

5 . The lipid particle of claim 3 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.

6 . The lipid particle of claim 5 , wherein the lipid particle consists essentially of

a. a lipid of claim 2 , or a salt or isomer thereof;

b. a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM;

c. sterol; and

d. PEG-DMG or PEG-DMA,

in a molar ratio of about 20-60% lipid of claim 2 :5-25% neutral lipid:25-55% sterol:0.5-15% PEG-DMG or PEG-DMA.

7 . The lipid particle of claim 3 , further comprising a therapeutic agent.

8 . The lipid particle of claim 7 , wherein the therapeutic agent is a nucleic acid.

9 . The lipid particle of claim 8 , wherein the nucleic acid is a plasmid.

10 . The lipid particle of claim 8 , wherein the nucleic acid is an immunostimulatory oligonucleotide.

11 . (canceled)

12 . The lipid particle of claim 8 , wherein the nucleic acid is an siRNA.

13 . A pharmaceutical composition comprising a lipid particle of claim 7 and a pharmaceutically acceptable excipient, carrier, or diluent.

14 . A method of modulating the expression of a target gene in a cell, comprising providing to a cell the lipid particle of claim 7 .

15 . (canceled)

16 . (canceled)

17 . A method of treating a disease or disorder characterized by overexpression of a polypeptide in a subject, comprising providing to the subject the pharmaceutical composition of claim 13 , wherein the therapeutic agent is selected from an siRNA, a microRNA, an antisense oligonucleotide, and a plasmid capable of expressing an siRNA, a microRNA, or an antisense oligonucleotide, and wherein the siRNA, microRNA, or antisense RNA comprises a polynucleotide that specifically binds to a polynucleotide that encodes the polypeptide, or a complement thereof.

18 . A method of treating a disease or disorder characterized by underexpression of a polypeptide in a subject, comprising providing to the subject the pharmaceutical composition of claim 13 , wherein the therapeutic agent is a plasmid that encodes the polypeptide or a functional variant or fragment thereof.

19 . A method of inducing an immune response in a subject, comprising providing to the subject the pharmaceutical composition of claim 13 , wherein the therapeutic agent is an immunostimulatory oligonucleotide.

20 . (canceled)

21 . A vaccine comprising the lipid particle of claim 7 .

22 . (canceled)

23 . (canceled)

24 . (canceled)

25 . (canceled)

26 . The lipid of claim 1 , or a salt or isomer thereof, wherein E is N(Q).

27 . The lipid of claim 2 , or a salt or isomer thereof, wherein E is N(Q).

28 . The lipid particle of claim 7 , wherein the therapeutic agent is mRNA.