Compositions and methods for polynucleotide transfection

1. A pharmaceutical composition comprising a peptide-polynucleotide complex, the peptide-polynucleotide complex comprising a ratio of peptide:polynucleotide that is more than about 50:1 and less than about 200:1, wherein the peptide is (a) non-lytic, non-cytotoxic, and capable of affecting the release of a polynucleotide from an endosome of a cell, and (b) comprises an amino acid sequence with (i) at least 80% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63, and (ii) two or more contiguous, basic amino acids (a cationic region) and one or more histidine residues located adjacent to the cationic region.

2. The composition of claim 1 , wherein the ratio of peptide to oligonucleotide is about 50:1 to about 100:1.

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

4. The composition of claim 1 , wherein the peptide comprises an amino acid sequence with at least 90% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63.

5. 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.

6. The composition of claim 1 , wherein the polynucleotide is a small interfering RNA (siRNA) or an microRNA (miRNA).

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

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

9. 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 ratio of peptide : polynucleotide that is more than about 50:1 and less than about 200:1, wherein the peptide is (a) non-lytic, non-cytotoxic, and capable of affecting the release of a polynucleotide from an endosome of a cell, and (b) comprises an amino acid sequence with (i) at least 80% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63, and (ii) two or more contiguous, basic amino acids (a cationic region) and one or more histidine residues located adjacent to the cationic region.

10. The method of claim 9 , 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.

11. The method of claim 9 , wherein:

(a) the polynucleotide disrupts a nucleotide normally associated with the NFκB signaling pathway and the subject needs therapeutic treatment for a tumor;

(b) the polynucleotide disrupts a nucleotide normally associated with the NFκB signaling pathway and the subject needs therapeutic treatment for arthritis;

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

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

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

12. A peptide comprising an amino acid sequence that has (a) at least 80% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63, and (b) two or more contiguous, basic amino acids (a cationic region) and one or more histidine residues located adjacent to the cationic region, wherein a therapeutically effective amount of the peptide is non-lytic, non-cytotoxic, and capable of affecting the release of a polynucleotide from an endosome of a cell.

13. The peptide of claim 12 , wherein the peptide comprises an amino acid sequence that has at least 90% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63.

14. The peptide of claim 13 , wherein the peptide comprises an amino acid sequence that has at least 95% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63.

15. The peptide of claim 14 , wherein the peptide comprises an amino acid sequence that has 100% identity to an amino acid sequence chosen from SEQ ID NO: 1, SEQ ID NO: 57 or SEQ ID NO: 63.