Dual Peptide-Mediated Targeted Delivery System

Patent metadata

Field	Value
Publication number	US-2016271258-A1
Application number	US-201615074698-A
Country	US
Kind code	A1
Filing date	Mar 18, 2016
Priority date	Mar 20, 2015
Publication date	Sep 22, 2016
Grant date	—

Abstract

This invention is generally related to a dual-peptide delivery system, where one peptide exhibits a receptor-targeting moiety and the other peptide exhibits an endosome-disruptive bioactivity.

First claim

What is claimed is:

1 . A composition comprising a dual peptide system for delivery of an agent comprising: 1) a first peptide comprising a targeting moiety and a stretch of densely packed cationic amino acid residues; 2) a second peptide having an endosome-disruptive activity and comprising a stretch of densely packed cationic amino acid residues; and 3) an agent.

2 . The composition of claim 1 , wherein the agent is a therapeutic agent.

3 . The composition of claim 2 , wherein the therapeutic agent is a nucleic acid molecule.

4 . The composition of claim 2 , wherein the therapeutic agent is selected from the group consisting of siRNA, microRNA, shRNA, antisense nucleic acid, ribozyme, killer-tRNAs, guide RNAs (part of the CRISPR/CAS system), long non-coding RNA, anti-miRNA oligonucleotide, and plasmid DNA.

5 . The composition of claim 1 , wherein the stretch of densely packed cationic amino acid residues comprises at least nine cationic residues.

6 . The composition of claim 5 , wherein the at least nine cationic residues are arginine residues.

7 . The composition of claim 5 , wherein the at least nine cationic residues are D-arginine residues.

8 . The composition of claim 1 , wherein the targeting moiety binds to a cell membrane receptor.

9 . The composition of claim 8 , wherein the cell membrane receptor is EGFR.

10 . The composition of claim 1 , wherein the first peptide is SEQ ID NO:1.

11 . The composition of claim 1 , wherein the second peptide is SEQ ID NO:2.

12 . The composition of claim 1 , wherein the first peptide is SEQ ID NO:1 and the second peptide is SEQ ID NO:2, further wherein the first peptide, second peptide, and agent is at a ratio of 60:30:1.

13 . The composition of claim 1 , wherein one or more peptides further comprise an additional modification to reduce renal clearance.

14 . The composition of claim 13 , wherein the additional modification is polyethylene glycol (PEG).

15 . The composition of claim 1 , further comprising one or more additional peptides.

16 . The composition of claim 15 , wherein the one or more additional peptides are anionic.

17 . The composition of claim 15 , wherein the one or more additional peptides comprise an additional modification.

18 . The composition of claim 17 , wherein the additional modification is polyethylene glycol (PEG).

19 . A method of administering an agent into a cell with minimal cytotoxicity, the method comprising contacting the cell with an effective amount of the composition of claim 1 .

20 . A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .

21 . The method of claim 20 , wherein the subject is human.

22 . The method of claim 20 , wherein the disease or disorder is cancer.

Assignees

• Musc Found For Res Dev
• Univ Clemson

Inventors

• Jakymiw Andrew
• Alexander-Bryant Angela

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · 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

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• C12N2320/32

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