Polyampholytes for delivering polyions to a cell
View Patent ↗An 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 polynucleotide into a cell, comprising:
a) forming a complex of polyampholyte containing a cleavable bond, wherein said bond is cleavable by a decrease in pH, and the polynucleotide; and,
b) delivering the complex to a cell.
2. The process of claim 1 wherein the polyampholyte contains maleamic acid.
3. The process of claim 1 wherein the polyampholyte is membrane-disruptive upon cleavage.
4. The process of claim 1 wherein the polynucleotide is delivered to a cell in vivo.
5. The process of claim 1 wherein the polynucleotide comprises an siRNA.
6. The process of claim 1 wherein the polynucleotide comprises an expression cassette encoding an siRNA.
7. The process of claim 1 wherein the polyampholyte comprises one or more polynucleotides covalently linked to a polycation.
8. The process of claim 7 wherein the polynucleotide is linked to the polycation via a labile linkage.
9. The process of claim 8 wherein the labile linkage consists of a disulfide bond.
10. The process of claim 7 wherein the polynucleotide comprises an siRNA.
11. A complex for delivering a polynucleotide to a cell, comprising: the polynucleotide and a cleavable polyampholyte wherein the polyion and the cleavable polyampholyte are bound in complex.
12. The complex of claim 11 wherein the cleavable polyampholyte contains maleamic acid.
13. The complex of claim 11 wherein the cleavable polyampholyte is membrane-disruptive upon cleavage.
14. The complex of claim 11 wherein the polynucleotide comprises an siRNA.
15. A composition for delivering a polyion to a cell comprising: the polyion linked to a second polyion of opposite charge to form a polyampholyte.
16. The composition of claim 15 wherein the linkage consists of a labile linkage.
17. The composition of claim 16 wherein the labile linkage consists of a disulfide bond.
18. The composition of claim 16 wherein the labile linkage consists of a bond that is cleavable by a decrease in pH.
19. The composition of claim 15 where the polyion consists of a polynucleotide.
20. The composition of claim 19 where the polynucleotide consists of an siRNA.