Lipid nanoparticles for delivery of nucleic acids
The application relates to cationic lipids and to compositions comprising said cationic lipids useful for the delivery of nucleic acids into living cells.
1 . A composition comprising
the cationic lipid of:
2 . The composition of claim 1 , further comprising one or more of the following excipients:
(i) a steroid;
(ii) a neutral lipid; and/or
(iii) a polymer conjugated lipid.
3 . The composition of claim 2 , further comprising a RNA.
4 . A kit or kit of parts, comprising the composition of claim 3 , and technical instructions providing information on administration and dosage of the components.
5 . The composition of claim 2 , wherein the composition comprises:
(i) a steroid;
(ii) a neutral lipid; and
(iii) a polymer conjugated lipid.
6 . The composition of claim 5 , wherein the composition comprises lipid nanoparticles (LNPs).
7 . The composition of claim 6 , wherein the steroid is cholesterol.
8 . The composition of claim 7 , wherein the neutral lipid is a zwitterionic compound.
9 . The composition of claim 6 , wherein the neutral lipid comprises 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE).
10 . The composition of claim 6 , wherein the composition further comprises 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC).
11 . The composition of claim 6 , wherein the polymer conjugated lipid is a compound according to formula (II):
P-A-L formula (II);
wherein P is a hydrophilic polymer moiety, A is an optional linker, and L is a lipid moiety.
12 . The composition of claim 6 , wherein the polymer conjugated lipid is a pegylated lipid.
13 . The composition of claim 6 , wherein the cationic lipid, the steroid, the neutral lipid and the polymer conjugated lipid are present in the composition in the following molar ratio: the cationic lipid at an amount of 30-70 mol %; the steroid at an amount of 20-50 mol %; the neutral lipid at an amount of 5-25 mol %; and the polymer conjugated lipid at an amount of 0.5-5 mol %.
14 . The composition of claim 6 , further comprising RNA in association with the LNPs.
15 . The composition of claim 14 , wherein the RNA is mRNA.
16 . The composition of claim 14 , wherein the RNA is self-replicating RNA.
17 . The composition of claim 14 , wherein the LNPs comprise the RNA in an amount such as to achieve an N/P ratio in the range of 10 to 20.
18 . The composition of claim 14 , wherein the LNPs comprise the RNA in an amount such as to achieve a lipid: RNA weight ratio in the range of 20 to 60.
19 . The composition of claim 14 , wherein the LNPs have a mean hydrodynamic diameter as determined by dynamic laser scattering from about 50 nm to about 300 nm.
20 . The composition of claim 14 , wherein the LNPs wherein the lipid nanoparticles exhibit a zeta potential in the range of −50 mV to +50 mV.