Polyanionic delivery of nucleic acids
Disclosed are dendritic anionic lipids which are compounds of Formula (I): wherein R and R 1 are non-polar groups, L is a linking moiety, and Dm is a dendritic moiety of m generations, each as defined herein. These dendritic anionic lipids are useful for delivery and expression of m RNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.
1. A compound selected from the group consisting of:
2. The compound of claim 1 , wherein said compound has the following structure:
3. The compound of claim 1 , wherein said compound has the following structure:
4. The compound of claim 1 , wherein said compound has the following structure:
5. A composition comprising an mRNA encoding a protein, encapsulated within a liposome, wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids, wherein at least one non-cationic lipid is the compound of claim 1 .
6. The composition of claim 5 , comprising an mRNA encoding for cystic fibrosis transmembrane conductance regulator (CFTR) protein.
7. The composition of claim 5 , comprising an mRNA encoding for ornithine transcarbamylase (OTC) protein.
8. A composition comprising a nucleic acid encapsulated within a liposome, wherein the liposome comprises the compound of claim 1 .
9. The composition of claim 8 , further comprising one more lipids selected from the group consisting of one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids.
10. The composition of claim 8 , wherein the nucleic acid is an mRNA encoding a peptide or polypeptide.
11. The composition of claim 10 , wherein the mRNA encodes a peptide or polypeptide for use in the delivery to or treatment of the lung of a subject or a lung cell.
12. The composition of claim 11 , wherein the mRNA encodes cystic fibrosis transmembrane conductance regulator (CFTR) protein.
13. The composition of claim 10 , wherein the mRNA encodes a peptide or polypeptide for use in the delivery to or treatment of the liver of a subject or a liver cell.
14. The composition of claim 13 , wherein the mRNA encodes ornithine transcarbamylase (OTC) protein.