Formation of polyampholytes in the presence of a polyion
View Patent ↗A polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.
1. A process for enhancing delivery of a polyion to a cell, comprising: forming a polyampholyte having a net charge, in the presence of a polyion; and, delivering the complex into a cell.
2. The process of claim 1 wherein the polyampholyte comprises a polycation selected from group consisting of (but not limited to) poly-L-lysine, poly-D-lysine, poly-L,D-lysine, polyethylenimine, polyallylamine, poly-L-ornithine, poly-D-ornithine, poly-L,D-ornithine, polyvinylamine, natural cationic protiens, synthetic cationic protiens, synthetic cationic peptides and synthetic polymers containing monomers with amines selected from but not limited to alkylamine, aryl amine, aralkylamine, imidazole, pyridine, and piperazine, pyrazine, pyrimidine, oxazoline, oxazole, oxazolidine. cationic polyvinylethers and their cationic copolymers.
3. The process of claim 1 wherein the polyampholyte comprises a polyanion.
4. The process of claim 3 wherein the polyanion comprises a molecule selected from the group consisting of poly-L-aspartic acid, poly-D-aspartic acid, poly-L,D-aspartic acid, polyacrylic acid, poly-L-glutamic acid, poly-D-glutamic acid, poly-L,D-glutamic acid, succinylated poly-L-lysine, succinylated poly-D-lysine, succinylated poly-L,D-lysine, succinylated polyethylenimine, succinylated polyallylamine, succinylated poly-L-ornithine, succinylated poly-D-ornithine, succinylated poly-L,D-ornithine, succinylated polyvinylamine, polymethacrylic acid, dextran sulfate, heparin, hyaluronic acid, DNA, RNA, natural anionic proteins, synthetic anionic proteins, synthetic anionic peptides, and synthetic polymers.
5. The process of claim 3 wherein the polyanion comprises a molecule selected from the group consisting of pegylated derivatives, pegylated derivatives carrying specific ligands, block copolymers, graft copolymers and hydrophilic polymers.
6. The process of claim 1 wherein the polyampholyte is delivered to a cell in vivo.
7. A complex for delivering a polyion to a cell, comprising: a polyion; and, a polyampholyte having a net charge.
8. The complex of claim 7 wherein the polyampholyte comprises a polycation.
9. The complex of claim 8 wherein the polycation is selected from group consisting of PLL and PEI.
10. The complex of claim 7 wherein the polyampholyte comprises a polyanion.
11. The complex of claim 10 wherein the polyanion comprises a molecule selected from the group consisting of succinylated PLL, succinylated PEI, polyglutamic acid, polyaspartic acid, polyacrylic acid, polymethacrylic acid, dextran sulfate, heparin, hyaluronic acid, DNA, RNA, and negatively charged proteins.
12. The complex of claim 11 wherein the polyanion comprises a molecule selected from the group consisting of pegylated derivatives, pegylated derivatives carrying specific ligands, block copolymers, graft copolymers and hydrophilic polymers.
13. A process for extravasation of a complex, comprising: forming a complex of polyion and polyampholyte having a net charge; and, inserting the complex into a vessel; delivering the complex to an extravascular space.
14. The complex of claim 13 wherein the polyampholyte comprises a polycation which is selected from group consisting of PLL and PEI.
15. The complex of claim 13 wherein the polyampholyte comprises a polyanion selected from the group consisting of succinylated PLL, succinylated PEI, polyglutamic acid, polyaspartic acid, polyacrylic acid, polymethacrylic acid, dextran sulfate, heparin, hyaluronic acid, DNA, RNA, and negatively charged proteins.
16. The complex of claim 15 wherein the negatively charged polyion comprises a molecule selected from the group consisting of pegylated derivatives, pegylated derivatives carrying specific ligands, block copolymers, graft copolymers and hydrophilic polymers.