Peptide-polynucleotide-hyaluronic acid nanoparticles and methods for polynucleotide transfection

1 . A pharmaceutical composition comprising a peptide-polynucleotide complex, the peptide-polynucleotide complex comprising:

a peptide;

a polynucleotide; and

hyaluronic acid;

wherein the peptide comprises an amino acid sequence which is at least 95% identical to the full-length amino acid sequence of SEQ ID NO: 1; and

wherein the peptide comprises one conservative amino acid substitution.

2 . The composition of claim 1 , wherein the peptide-polynucleotide complex is about 10 nm to about 150 nm in diameter.

3 . The composition of claim 2 , wherein the peptide-polynucleotide complex is about 10 nm to about 50 nm in diameter.

4 . The composition of claim 1 , wherein the hyaluronic acid coats the peptide-polynucleotide complex.

5 . The composition of claim 1 , wherein the hyaluronic acid is integrated into the peptide-polynucleotide complex.

6 . The composition of claim 1 , wherein the polynucleotide is an RNA.

7 . The composition of claim 1 , wherein the polynucleotide is an mRNA.

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 non-coding RNA is an siRNA.

10 . The composition of claim 8 , wherein the non-coding RNA is an miRNA.

11 . The composition of claim 1 , wherein the peptide is cationic.

12 . The composition of claim 1 , wherein the peptide-polynucleotide complex comprises a ratio of peptide:polynucleotide that is more than about 50:1 and less than about 200:1.

13 . A method of delivering a polynucleotide to the cytoplasm of a cell, the method comprising: contacting a cell with the composition of claim 1 .

14 . A method of treating osteoarthritis in a subject, comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .