Peptide-polynucleotide complex for polynucleotide transfection

1. A pharmaceutical composition comprising a peptide-polynucleotide complex, the peptide-polynucleotide complex comprising a molar ratio of peptide:polynucleotide that is less than 50:1, wherein the peptide is (a) non-lytic and capable of affecting the release of a polynucleotide from an endosome of a cell, and (b) comprises an amino acid sequence with at least 80% identity to the amino acid sequence of SEQ ID NO: 1.

2. The composition of claim 1 , wherein the molar ratio of peptide to oligonucleotide is chosen from about 5:1 to about 45:1.

3. The composition of claim 2 , wherein the molar ratio of peptide to oligonucleotide is about 5:1 to about 35:1, about 10:1 to about 40:1, or about 15:1 to about 45:1.

4. The composition of claim 2 , wherein the molar ratio of peptide to oligonucleotide is about 5:1 to about 25:1, about 10:1 to about 30:1, about 15:1 to about 35:1, or about 20:1 to about 40:1, or about 25:1 to about 45:1.

5. The composition of claim 1 , wherein the complex is a nanoparticle with a diameter of about 50 nm to about 200 nm.

6. The composition of claim 1 , wherein the peptide comprises an amino acid sequence with at least 90% identity to SEQ ID NO: 1.

7. The composition of claim 1 , wherein the peptide comprises at least one cationic region and at least one histidine residue located adjacent to or within at least one cationic region of the peptide wherein a cationic region is two or more contiguous basic amino acids.

8. The composition of claim 1 , wherein the polynucleotide is a non-coding RNA capable of regulating or inhibiting the expression of a nucleic acid sequence.

9. The composition of claim 8 , wherein the polynucleotide is a small interfering RNA (siRNA) or an microRNA (miRNA).

10. The composition of claim 1 , wherein the complex is coated with albumin.

11. The composition of claim 1 , wherein the polynucleotide of the complex disrupts expression of at least one nucleic acid sequence encoding a protein selected from the group consisting of STAT3, JNK2, p65, and p100/52.

12. A method of delivering a polynucleotide to the cytoplasm of a cell, the method comprising contacting a cell with a peptide-polynucleotide complex, the peptide-polynucleotide complex comprising a molar ratio of peptide:polynucleotide that is less than 50:1, wherein the peptide is (a) non-lytic and capable of affecting the release of a polynucleotide from an endosome of a cell, and (b) comprises an amino acid sequence with at least 80% identity to the amino acid sequence of SEQ ID NO: 1.

13. The method of claim 12 , wherein the molar ratio of peptide to oligonucleotide is about 5:1 to about 35:1, about 10:1 to about 40:1, or about 15:1 to about 45:1.

14. The method of claim 12 , wherein the molar ratio of peptide to oligonucleotide is about 5:1 to about 25:1, about 10:1 to about 30:1, about 15:1 to about 35:1, or about 20:1 to about 40:1, or about 25:1 to about 45:1.

15. The method of claim 12 , wherein the polynucleotide is delivered to the cytoplasm of a cell in a subject in need thereof and the method comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising the peptide-polynucleotide complex.

16. The method of claim 15 , wherein:

(a) the polynucleotide disrupts STAT3 expression in a cell and the subject needs therapeutic treatment to inhibit angiogenesis;

(b) the polynucleotide disrupts JNK2 expression in a cell and the subject needs therapeutic treatment to inhibit foam cell formation; or

(c) the polynucleotide disrupts p65 expression in a cell and the subject needs therapeutic treatment for arthritis.

17. A peptide comprising an amino acid sequence that has at least 80% identity to the amino acid sequence of SEQ ID NO: 1, wherein the peptide is non-lytic and capable of affecting the release of a polynucleotide from an endosome of a cell.

18. The peptide of claim 17 , wherein the peptide comprises an amino acid sequence has at least 90% identity to the amino acid sequence of SEQ ID NO: 1.

19. The peptide of claim 17 , wherein the peptide comprises an amino acid sequence has at least 95% identity to the amino acid sequence of SEQ ID NO: 1.

20. The peptide of claim 17 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 1.