Method of preventing aggregation of a lipid:nucleic acid complex
View Patent ↗Particle aggregation of lipid:nucleic acid complex particles is prevented by incorporating a non-cationic lipid into lipid:nucleic acid complex particles containing a cationic lipid and a nucleic acid polymer. The non-cationic lipid is a polyethylene glycol-based polymer.
1. A method of preventing particle aggregation of lipid:nucleic acid complex particles, said method comprising the step of incorporating an non-cationic lipid into lipid:nucleic acid complex particles comprising a cationic lipid and a nucleic acid polymer, wherein said additional lipid is a polyethylene glycol-based polymer.
2. The method of claim 1 , wherein the polyethylene glycol-based polymer is selected from the group consisting of polyethylene glycol lipids, polyethylene glycol ceramides and ganglioside-modified lipids.
3. The method of claim 1 , wherein the amount of additional lipid is from 1 to 15% of the particles.
4. The method of claim 1 , wherein said nucleic acid is selected from the group consisting of DNA and RNA.
5. The method of claim 1 , wherein said nucleic acid is DNA.
6. The method of claim 1 , wherein said lipid:nucleic acid complex is lyophilized.
7. The method of claim 1 , wherein the nucleic acid is linked to an expression vector to facilitate gene expression after entry into a cell.
8. A method of preparing a lipid:nucleic acid complex, comprising the steps of:
(a) combining a nucleic acid with a cationic lipid to produce a lipid:nucleic acid complex; and
(b) mixing the lipid:nucleic acid complex with a non-cationic lipid which is a polyethylene glycol-based polymer, wherein the polyethylene glycol-based lipid reduces the tendency of the lipid:nucleic acid complex to aggregate.
9. The method of claim 8 , wherein the polyethylene glycol-based polymer is selected from the group consisting of polyethylene glycol lipids, polyethylene glycol ceramides and ganglioside-modified lipids.
10. The method of claim 8 , wherein the amount of non-cationic lipid is from 1 to 15%.
11. The method of claim 8 , wherein said nucleic acid is selected from the group consisting of DNA and RNA.
12. The method of claim 8 , wherein said nucleic acid is DNA.
13. The method of claim 8 , wherein said lipid:nucleic acid complex is lyophilized.
14. The method of claim 8 , wherein the nucleic acid is linked to an expression vector to facilitate gene expression after entry into a cell.