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 an amino-lipid of claim 1 and an additional lipid selected from the group consisting of: cationic lipid, helper lipid, and PEG-lipid.
3. The lipid nanoparticle of claim 2 further comprising a hydrophobic small molecule.
4. The lipid nanoparticle of claim 2 further comprising a biologically active compound.
5. The lipid nanoparticle of claim 4 wherein the biologically active compound is selected from the group consisting of: small molecule, peptide, protein, carbohydrate, nucleic acid, and lipid.
6. The lipid nanoparticle of claim 2 , wherein the cationic lipid is a lipid comprising a quaternary amine with a nitrogen atom having four organic substituents.
7. The lipid nanoparticle of claim 2 , wherein the helper lipid is a neutral zwitterionic lipid.
8. The lipid nanoparticle of claim 3 , wherein the hydrophobic small molecule is selected from the group consisting of: a sterol and a hydrophobic vitamin.
9. The lipid nanoparticle of claim 3 , wherein the hydrophobic small molecule is cholesterol.
10. The lipid nanoparticle of claim 5 , wherein the peptide is a cell penetrating peptide.
11. The lipid nanoparticle of claim 5 , wherein the protein is selected from the group consisting of nucleoprotein, mucoprotein, lipoprotein, synthetic polypeptide, a small molecule linked to a protein, and glycoprotein.
12. The lipid nanoparticle of claim 5 , 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 5 , 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.