High sterol-containing lipid nanoparticles
The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 3 mol %, wherein each mol % content is relative to total lipid present in the lipid nanoparticle.
1. A lipid nanoparticle comprising:
a nucleic acid cargo molecule;
a sterol or a derivative thereof present at a mol % content between 49 mol % and 85 mol %;
a phospholipid content of 4 mol % or less;
an ionizable lipid content that is less than 40 mol %; and
a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 2.5 mol %,
wherein each mol % content is relative to total lipid present in the lipid nanoparticle.
2. The lipid nanoparticle of claim 1 , wherein the sterol or the derivative thereof is present at a content of at least 50 mol %.
3. The lipid nanoparticle of claim 1 , wherein the sterol or the derivative thereof is present at a content of at least 52 mol %.
4. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is present at a content that is less than 38.5 mol %.
5. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is present at a content that is less than 35.5 mol %.
6. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is present at a content that is less than 34.5 mol %.
7. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is present at a content that is less than 33.5 mol %.
8. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is present at a content that is less than 32.5 mol %.
9. The lipid nanoparticle of claim 1 , wherein the cargo molecule is siRNA, mRNA, vector nucleic acid, an antisense oligonucleotide or is a nucleic acid-protein or peptide complex.
10. The lipid nanoparticle of claim 1 , wherein the cargo molecule is siRNA, vector nucleic acid or an antisense oligonucleotide.
11. The lipid nanoparticle of claim 1 , wherein the ionizable lipid is an amino lipid.
12. The lipid nanoparticle of claim 1 , wherein the sterol derivative is a non-cationic lipid.
13. The lipid nanoparticle of claim 1 , wherein the sterol is cholesterol or the sterol derivative is a cholesterol derivative.
14. The lipid nanoparticle of claim 1 , wherein the phospholipid is present at 0.5 to 3 mol %.
15. The lipid nanoparticle of claim 14 , wherein the phospholipid is a phospholipid- cholesterol conjugate.
16. The lipid nanoparticle of claim 15 , wherein the phospholipid-cholesterol conjugate is a phosphatidylcholine-cholesterol conjugate.