Lipids and compositions for intracellular delivery of biologically active compounds
The present invention provides novel amino-lipids, compositions comprising such amino-lipids and methods of producing them. In addition, lipid nanoparticles comprising the novel amino-lipids and a biologically active compound are provided, as well as methods of production and their use for intracellular drug delivery.
1. A linear amino-lipid having the structure:
2. A lipid nanoparticle comprising the linear amino lipid of claim 1 .
3. The lipid nanoparticle of claim 2 , further comprising an additional lipid selected from the group consisting of: a cationic lipid, a helper lipid, and a PEG-lipid.
4. The lipid nanoparticle of claim 3 , further comprising a hydrophobic small molecule.
5. The lipid nanoparticle of claim 3 , further comprising a biologically active compound.
6. The lipid nanoparticle of claim 5 , wherein the biologically active compound is selected from the group consisting of: a small molecule, a peptide, a protein, a carbohydrate, a nucleic acid, and a lipid.
7. The lipid nanoparticle of claim 3 , wherein the cationic lipid is a lipid comprising a quaternary amine with a nitrogen atom having four organic substituents.
8. The lipid nanoparticle of claim 3 , wherein the helper lipid is a neutral zwitterionic lipid.
9. The lipid nanoparticle of claim 4 , wherein the hydrophobic small molecule is selected from the group consisting of a sterol and a hydrophobic vitamin.
10. The lipid nanoparticle of claim 9 , wherein the hydrophobic small molecule is cholesterol.
11. The lipid nanoparticle of claim 6 , wherein the protein is selected from the group consisting of a nucleoprotein, a mucoprotein, a lipoprotein, a synthetic polypeptide, a small molecule linked to a protein and a glycoprotein.
12. The lipid nanoparticle of claim 6 , wherein the nucleic acid is in the form of a single stranded or partially double stranded oligomer or a polymer composed of ribonucleotides.
13. The lipid nanoparticle of claim 6 , wherein the nucleic acid is selected from the group consisting of miRNA, antisense oligonucleotides, siRNA, immune-stimulatory oligonucleotides, aptamers, ribozymes, and plasmids encoding a specific gene or siRNA.
14. A pharmaceutical composition comprising a linear amino-lipid having the structure:
15. The pharmaceutical composition of claim 14 , further comprising a biologically active compound.
16. The pharmaceutical composition of claim 15 , wherein the biologically active compound is a nucleic acid.
17. The pharmaceutical composition of claim 16 , wherein the nucleic acid is in the form of a single stranded or partially double stranded oligomer or a polymer composed of ribonucleotides.
18. A method of treating a disease that is caused by the over-expression of one or several proteins in a subject, said method comprising the administration of a lipid nanoparticle according to claim 5 to the subject.
19. A method of treating a disease that is caused by a reduced, suppressed or missing expression of one or several proteins in a subject, said method comprising the administration of a lipid nanoparticle according to claim 5 to the subject.
20. A method for generating an immune response in a subject, said method comprising the administration of a lipid nanoparticle according to claim 5 to the subject, wherein the biologically active compound is an immune-stimulatory nucleic acid.