COMPOSITIONS FOR NUCLEIC ACID DELIVERY

1 . A compound having the formula:

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 alkoxy, optionally substituted C 10 -C 30 alkenyl, optionally substituted C 10 -C 30 alkenyloxy, optionally substituted C 10 -C 30 alkynyl, optionally substituted C 10 -C 30 alkynyloxy, or optionally substituted C 10 -C 30 acyl;

represents a connection between L 2 and L 1 which is:

(1) a single bond between one atom of L 2 and one atom of L 1 , wherein

L 1 is C(R x ) or N;

L 2 is —CR 5 R 6 —, —O—, —S—, —N(Q)-,

═C(R 5 )—, —C(O)N(Q)-, —C(O)O—, —N(Q)C(O)—, —OC(O)—, or —C(O)—;

(2) a double bond between one atom of L 2 and one atom of L 1 ; wherein

L 1 is C;

L 2 is —CR 5 ═, —N(Q)=, —N—, —O—N═, —N(Q)-N═, or —C(O)N(Q)-N═;

(3) a single bond between a first atom of L 2 and a first atom of L 1 , and a single bond between a second atom of L 2 and the first atom of L 1 , wherein

L 1 is C;

L 2 has the formula

wherein

X is the first atom of L 2 , Y is the second atom of L 2 , represents a single bond to the first atom of L 1 , and X and Y are each, independently, selected from the group consisting of —O—, —S—, alkylene, —N(Q)-, —C(O)—, —O(CO)—, —OC(O)N(Q)-, —N(Q)C(O)O—, —C(O)O, —OC(O)O—, —OS(O)(Q 2 )O—, and —OP(O)(Q 2 )O—;

Z 1 and Z 4 are each, independently, —O—, —S—, —CH 2 —, —CHR 5 —, or —CR 5 R 5 —;

Z 2 is CH or N;

Z 3 is CH or N;

or Z 2 and Z 3 , taken together, are a single C atom;

A 1 and A 2 are each, independently, —O—, —S—, —CH 2 —, —CHR 5 —, or —CR 5 R 5 —;

each Z is N, C(R 5 ), or C(R 3 );

k is 0, 1, or 2;

each m, independently, is 0 to 5;

each n, independently, is 0 to 5;

where m and n taken together result in a 3, 4, 5, 6, 7 or 8 member ring;

(4) a single bond between a first atom of L 2 and a first atom of L 1 , and a single bond between the first atom of L 2 and a second atom of L 1 , wherein

(A) L 1 has the formula:

wherein

X is the first atom of L 1 , Y is the second atom of L 1 , represents a single bond to the first atom of L 2 , and X and Y are each, independently, selected from the group consisting of —O—, —S—, alkylene, —N(Q)-, —C(O)—, —O(CO)—, —OC(O)N(Q)-, —N(Q)C(O)O—, —C(O)O, —OC(O)O—, —OS(O)(Q 2 )O—, and —OP(O)(Q 2 )O—;

T 1 is CH or N;

T 2 is CH or N;

or T 1 and T 2 taken together are C═C;

L 2 is CR 5 ; or

(B) L 1 has the formula:

wherein

X is the first atom of L 1 , Y is the second atom of L 1 , represents a single bond to the first atom of L 2 , and X and Y are each, independently, selected from the group consisting of —O—, —S—, alkylene, —N(Q)-, —C(O)—, —O(CO)—, —OC(O)N(Q)-, —N(Q)C(O)O—, —C(O)O, —OC(O)O—, —O S(O)(Q 2 )O—, and —OP(O)(Q 2 )O—;

T 1 is —CR 5 R 5 —, —N(Q)-, —O—, or —S—;

T 2 is —CR 5 R 5 —, —N(Q)-, —O—, or —S—;

L 2 is CR 5 or N;

R 3 has the formula:

wherein

each of Y 1 , Y 2 , Y 3 , and Y 4 , independently, is alkyl, cycloalkyl, aryl, aralkyl, or alkynyl; or

any two of Y 1 , Y 2 , and Y 3 are taken together with the N atom to which they are attached to form a 3- to 8-member heterocycle; or

Y 1 , Y 2 , and Y 3 are all be taken together with the N atom to which they are attached to form a bicyclic 5- to 12-member heterocycle;

each R n , independently, is H, halo, cyano, hydroxy, amino, alkyl, alkoxy, cycloalkyl, aryl, heteroaryl, or heterocyclyl;

L 3 is a bond, —N(Q)-, —O—, —S—, —(CR 5 R 6 ) a —, —C(O)—, or a combination of any two of these;

L 4 is a bond, —N(Q)-, —O—, —S—, —(CR 5 R 6 ) a —, —C(O)—, or a combination of any two of these;

L 5 is a bond, —N(Q)-, —O—, —S—, —(CR 5 R 6 ) a —, —C(O)—, or a combination of any two of these;

each occurrence of R 5 and R 6 is, independently, H, halo, cyano, hydroxy, amino, alkyl, alkoxy, cycloalkyl, aryl, heteroaryl, or heterocyclyl; or two R 5 groups on adjacent carbon atoms are taken together to form a double bond between their respective carbon atoms; or two R 5 groups on adjacent carbon atoms and two R 6 groups on the same adjacent carbon atoms are taken together to form a triple bond between their respective carbon atoms;

each a, independently, is 0, 1, 2, or 3;

wherein

an R 5 or R 6 substituent from any of L 3 , L 4 , or L 5 is optionally taken with an R 5 or R 6 substituent from any of L 3 , L 4 , or L 5 to form a 3- to 8-member cycloalkyl, heterocyclyl, aryl, or heteroaryl group; and

any one of Y 1 , Y 2 , or Y 3 , is optionally taken together with an R 5 or R 6 group from any of L 3 , L 4 , and L 5 , and atoms to which they are attached, to form a 3- to 8-member heterocyclyl group;

each Q, independently, is H, alkyl, acyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocyclyl; and

each Q 2 , independently, is O, S, N(Q)(Q), alkyl or alkoxy.

2 . The compound of claim 1 represented by formula I:

wherein,

X and Y are each independently —O—, —S—, alkylene, —N(Q)-, —C(O)—, —O(CO)—, —OC(O)N(Q)-, —N(Q)C(O)O—, —C(O)O, —OC(O)O—, —OS(O)(Q 2 )O—, or —OP(O)(Q 2 )O—;

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

Q 2 is independently for each occurrence O, S, N(Q)(Q), alkyl or alkoxy;

A 1 and A 2 are each independently —O—, —S—, —CH 2 —, —CHR 5 —, —CR 5 R 5 —;

Z is N or C(R 3 );

each R′, R″, and R″′, independently, is H, alkyl, alkyl, heteroalkyl, aralkyl, cyclic alkyl, or heterocyclyl;

R 5 is H, halo, cyano, hydroxy, amino, optionally substituted alkyl, optionally substituted alkoxy, or optionally substituted cycloalkyl;

i and j are each independently 0-10;

a and b are each independently 0-2;

and R 1 , R 2 and R 3 are as defined in claim 1 .

3 . The compound of claim 2 , selected from the group consisting of:

4 . The compound of claim 1 represented by formula XXXIII:

wherein,

E is each independently for each

occurrence —CH 2 —, —O—, —S—, —SS—, —CO—, —C(O)O—, —C(O)N(R′)—, —OC(O)N(R′)—, —N(R′)C(O)N(R″)—, —C(O)—N(R′)—N═C(R″′)—; —N(R′)—N═C(R″)—, —O—N═C(R″)—, —C(S)O—, —C(S)N(R′)—, —OC(S)N(R′)—, —N(R′)C(S)N(R″)—, —C(S)—N(R′)—N═C(R″′); —S—N═C(R″); —C(O)S—, —SC(O)N(R′)—, —OC(O)—, —N(R′)C(O)—, —N(R′)C(O)O—, —C(R″′)═N—N(R′)—; —C(R″′)═N—N(R′)— C(O)—, —C(R″′)═N—O—, —OC(S)—, —SC (O)—, —N(R′)C(S)—, —N(R′)C(S)O—, —N(R′)C(O)S—, —C(R″′)═N—N(R′)—C(S)—, —C(R″″)═N—S—, C[═N(R′)]O, C[═N(R′)]N(R″), —OC[═N(R′)]—, —N(R″)C[═N(R′)]N(R″′)—, —N(R″)C[═N(R′)]—,

arylene, heteroarylene, cycloalkylene, or heterocyclylene;

each R′, R″, and R″′, independently, is H, alkyl, alkyl, heteroalkyl, aralkyl, cyclic alkyl, or heterocyclyl;

and R 1 , R 2 and R 3 are as defined in claim 1 .

5 . The compound of claim 4 , wherein E is O(CO), (CO)O, OC(O)N(R′), or N(R′)C(O)O.

6 . The compound of claim 2 , selected from the group consisting of:

7 . A method for delivering a nucleic acid to a cell comprising contacting cells with a compound according to claim 1 .

8 . (canceled)

9 . The method of claim 7 , wherein the composition further comprises a nucleic acid.

10 - 14 . (canceled)

15 . The method of claim 9 , wherein the nucleic acid includes a chemically modified nucleic acid.

16 - 20 . (canceled)

21 . The method of claim 9 , wherein the nucleic acid is siRNA.

22 . The method of claim 9 , wherein the nucleic acid is mRNA.

23 . (canceled)

24 . A storage-stable composition comprising

a cryoprotectant selected from sucrose, trehalose, glucose, 2-hydroxypropyl-α-cyclodextrin, and sorbitol, and

a compound according to claim 1 .

25 . The composition of claim 24 , further comprising a neutral lipid.

26 . The composition of claim 24 , further comprising a sterol.

27 . The composition of claim 24 , further comprising a lipid capable of reducing aggregation.

28 . The composition of claim 24 , further comprising a nucleic acid.

29 . The composition of claim 24 , wherein the cryoprotectant is present at from 5 wt % to 25 wt %.

30 . The composition of claim 24 , wherein the cryoprotectant is present at from 7 wt % to 15 wt %.

31 . The composition of claim 24 , wherein the cryoprotectant includes sucrose.

32 . (canceled)

33 . The composition of claim 28 , wherein the composition is lyophilized.

34 - 36 . (canceled)