Peptide, complex of peptide and siRNA and use thereof

Patent metadata

Field	Value
Publication number	US-10076575-B2
Application number	US-201415106108-A
Country	US
Kind code	B2
Filing date	Dec 18, 2014
Priority date	Dec 18, 2013
Publication date	Sep 18, 2018
Grant date	Sep 18, 2018

Abstract

A series of peptides and a peptide-siRNA complex are disclosed, wherein the peptide based complex effectively enhances delivery of siRNA molecules into the cells and release of siRNA in the cell, and improves siRNA mediated gene silencing efficiency of cellular targets. Pharmaceutical compositions that include the complex, as well as a use of the complex in the gene therapy field, are also disclosed.

First claim

The invention claimed is:

1. A peptide comprising a hydrophobic part and a hydrophilic part, wherein the hydrophilic part comprises a positively charged amino acid residue, and wherein the peptide is SEQ ID NO:10.

2. The peptide according to claim 1 , wherein a nitrogen terminal of the peptide is acetylated, and a carbon terminal of the peptide is amidated.

3. A peptide comprising a hydrophobic part and a hydrophilic part, wherein the hydrophilic part comprises a positively charged amino acid residue, wherein the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:10.

4. A peptide comprising a hydrophobic part and a hydrophilic part, wherein the hydrophilic part comprises a positively charged amino acid residue, wherein the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:11.

5. A peptide comprising a hydrophobic part and a hydrophilic part, wherein the hydrophilic part comprises a positively charged amino acid residue, wherein the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:12.

6. A complex comprising:
a cargo molecule; and
a peptide comprising a hydrophobic part and a hydrophilic part, wherein the hydrophilic part comprises a positively charged amino acid residue, and wherein at least one of:
(a) the peptide is SEQ ID NO:10;
(b) the peptide is SEQ ID NO:10, and wherein a nitrogen terminal of the peptide is acetylated, and a carbon terminal of the peptide is amidated;
(c) the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:10;
(d) the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:11; and
(e) the peptide is CH 3 (CH 2 ) 16 CONH—B—CONH 2 , and wherein the B is SEQ ID NO:12.

7. The complex according to claim 6 , wherein the cargo molecule and the peptide are coupled non-covalently.

8. The complex according to claim 6 , wherein the particle size of the complex is ranged from 20 nm to 999 nm.

9. The complex according to claim 6 , wherein the cargo molecule is a nucleic acid.

10. The complex according to claim 9 , wherein the nucleic acid is a short interfering RNA (siRNA).

11. The complex according to claim 10 , wherein the siRNA is complexed with the peptide at a molar ratio within the range of 1:1 to 80:1.

12. The complex according to claim 10 , wherein the siRNA is complexed with the peptide at a molar ratio of 20:1.

13. The complex according to claim 10 , wherein the siRNA is complexed with the peptide at a molar ratio of 40:1.

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

15. A pharmaceutical composition comprising a complex according to claim 6 .

16. A kit used to deliver drugs to a patient, wherein the kit comprises:
a pharmaceutical composition according to claim 15 ;
one or more electrolytes;
buffers;
a delivery device; and
a container adapted to mix one or more other agents together.

Assignees

• Positec Power Tools Suzhou Co Ltd
• Chen Pu

Inventors

• Chen Pu
• Chu Dafeng
• Chen Baoling
• Xu Wen
• Pan Ran

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/113 Primary

  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

• A61K9/5169

  Proteins, e.g. albumin, gelatin · CPC title

• C07K14/47

  from mammals · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title