Peptide Sequence Design and Use Thereof For Peptide-Mediated siRNA Delivery

Patent metadata

Field	Value
Publication number	US-2017128582-A1
Application number	US-201715407802-A
Country	US
Kind code	A1
Filing date	Jan 17, 2017
Priority date	Nov 24, 2011
Publication date	May 11, 2017
Grant date	—

Abstract

Peptides that have been found to facilitate the delivery of siRNA molecules into cells and to function in siRNA mediated silencing of cellular targets are disclosed. Complexes that include one of the peptides and a cargo molecule are disclosed, wherein the peptide and the cargo molecule are coupled non-covalently. Also disclosed are methods of producing and using the peptides/complexes.

First claim

What is claimed is:

1 . A complex comprising:
a peptide having the amino acid sequence according to any one of SEQ ID NOs: 40 to 42; and a cargo molecule.

2 . The complex according to claim 1 , wherein the cargo molecule is a nucleic acid.

3 . The complex according to claim 2 , wherein the nucleic acid is short interfering RNA (siRNA).

4 . The complex of claim 3 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 1:1 to 60:1.

5 . The complex of claim 3 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 5:1 to 60:1.

6 . The complex of claim 3 , wherein the siRNA is complexed with the peptide at a molar ratio of 20:1.

7 . The complex of claim 3 , wherein the siRNA is complexed with the peptide at a molar ratio of 40:1.

8 . A pharmaceutical composition comprising a complex according to claim 3 for delivering a therapeutically effective amount of siRNA.

9 . The pharmaceutical composition of claim 8 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 1:1 to 60:1.

10 . A method of reducing the levels of a gene product within a cell or tissue of an animal comprising:
administering the pharmaceutical composition of claim 8 .

11 . The method of claim 10 , wherein the cell is a tumor cell or the tissue is tumor tissue.

12 . The method of claim 10 , wherein the siRNA targets a gene product that regulates apoptosis.

13 . The method of claim 12 , wherein the gene that regulates apoptosis is bcl-2.

14 . The method of claim 10 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 1:1 to 60:1.

15 . A method of delivering siRNA into a cell, comprising:
administering the complex of claim 3 to the cell.

16 . The method of claim 15 , wherein the cell is a CHO cell.

17 . The method of claim 15 , wherein the siRNA reduces the levels of an endogenous protein of the cell.

18 . The method of claim 15 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 1:1 to 60:1.

Assignees

• Chen Pu
• Positec Power Tools Suzhou Co Ltd

Inventors

• Chen Pu
• Jafari Mousa
• Xu Wen
• Chen Baoling
• Pan Ran
• Karunaratne Nedra

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07K14/4723

  Cationic antimicrobial peptides, e.g. defensins · CPC title