NANOMATERIALS
Lipid nanoparticle compositions for delivery of nucleic acids are described. The lipid nanoparticle may contain a conformationally constrained ionizable lipid as part of the composition. These compositions may allow for delivery of cargo without the need for a targeting ligand.
1 .- 22 . (canceled)
23 . A compound of Formula (IIb):
wherein:
R 9 is C 9 -C 20 alkyl optionally fused with 1-4 C 3 -C 6 cycloalkyl groups, C 9 -C 20 alkenyl with 1-3 units of unsaturation, or —(CH 2 ) g —X 17 , wherein X 17 is optionally substituted C 4 -C 12 cycloalkyl;
f is independently an integer from 0-6;
R 16 is hydrogen or optionally substituted C 5 -C 6 aryl;
X 15 is optionally substituted C 4 -C 12 cycloalkyl or optionally substituted C 5 -C 10 aryl; and
X 16 is hydrogen or optionally substituted C 4 -C 12 cycloalkyl;
provided that when f is 1 and R 9 is
X 15 is not
24 . The compound of claim 23 , wherein the compound is selected from the group consisting of:
25 . The compound of claim 24 , having the following structure
26 . The compound of claim 24 , having the following structure
27 . The compound of claim 24 , having the following structure
28 . The compound of claim 24 , having the following structure
29 . The compound of claim 24 , having the following structure
30 . The compound of claim 24 , having the following structure
31 . The compound of claim 24 , having the following structure
32 . The compound of claim 24 , having the following structure
33 . The compound of claim 24 , having the following structure
34 . A lipid nanoparticle composition comprising:
an ionizable lipid that is the compound of claim 23 ;
a phospholipid;
a polyethylene glycol-lipid; and
a cholesterol.
35 . The lipid nanoparticle composition of claim 23 , further comprising a nucleic acid.
36 . The lipid nanoparticle composition of claim 34 , wherein the amount of ionizable lipid is present in the range of about 35 to 65 mole percent, based on total moles.
37 . The lipid nanoparticle composition of claim 34 , wherein the phospholipid is DSPC.
38 . The lipid nanoparticle composition of claim 34 , wherein the phospholipid is DMPC.
39 . A method of delivering a nucleic acid to a subject in need thereof, comprising administering to the subject the lipid nanoparticle composition of claim 34 .
40 . The lipid nanoparticle composition of claim 35 , wherein the nucleic acid is siRNA, miRNA, anti-sense oligonucleotide, or immunostimulatory oligonucleotide.
41 . The lipid nanoparticle composition of claim 34 , wherein the polyethylene glycol-lipid is DMG-PEG2000.
42 . The lipid nanoparticle composition of claim 34 , wherein the polyethylene glycol-lipid is DSG-PEG2000.