pH-titratable polyampholytes for delivering polyions to a cell
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:
a) forming a complex of polyion and polyampholyte that is pH-titratable at physiological pH; and,
b) delivering the complex into a cell.
2. The process of claim 1 wherein the polyion is DNA.
3. The process of claim 1 wherein the polyampholyte contains imidazole groups.
4. The process of claim 1 wherein the polyampholyte contains imidazole derivatives.
5. The process of claim 1 wherein the polyampholyte is anionic at pH 8.
6. The process of claim 1 wherein the polyampholyte is membrane active.
7. The process of claim 1 wherein the polyampholyte is delivered to a cell in vivo.
8. A complex for delivering a polyion to a cell, comprising: a polyion; and, a polyampholyte that is pH-titratable at physiological pH.
9. The complex of claim 8 wherein the polyion is DNA.
10. The complex of claim 8 wherein the polyampholyte contains imidazole groups.
11. The complex of claim 8 wherein the polyampholyte contains imidazole derivatives.
12. The complex of claim 8 wherein the polyampholyte is anionic at pH 8.
13. The complex of claim 8 wherein the polyampholyte is membrane active.
14. A process for extravasation of a complex, comprising:
a) forming a complex of polyion and polyampholyte wherein the polyampholyte is pH-titratable at physiological pH;
b) inserting the complex into a vessel; and,
c) delivering the complex to an extravascular space.
15. The process of claim 14 wherein the polyion is DNA.
16. The process of claim 14 wherein the polyampholyte contains imidazole groups.
17. The process of claim 14 wherein the polyampholyte contains imidazole derivatives.
18. The process of claim 14 wherein the polyampholyte is membrane active.
19. The process of claim 15 wherein the DNA is expressed in an extravascular cell.
20. The process of claim 14 wherein the polyampholyte is anionic at pH 8.