Positively charged polysaccharides for RNA transfection

Patent metadata

Field	Value
Publication number	US-9566346-B2
Application number	US-201414765790-A
Country	US
Kind code	B2
Filing date	Feb 5, 2014
Priority date	Feb 5, 2013
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

A complex includes RNA and a positively charged modified polysaccharide selected from starch, amylose, amylopectin, galactan, chitosan, or dextrin. The complex can be formed into a pharmaceutical composition. The complex can be used in methods for RNA transfection, gene therapy and treatment of a disease, disorder or condition. The positively charged modified polysaccharide can be used in connection with RNA transfection into cells.

First claim

What is claimed is:

1. A complex for the delivery of a siRNA or miRNA, comprising the siRNA or miRNA complexed with a quaternized polysaccharide, said polysaccharide being selected from the group consisting of starch, amylose, amylopectin, galactan and dextrin.

2. The complex of claim 1 , wherein the molar ratio of positively charged amine groups on said quaternized polysaccharide and negatively charged phosphates on said siRNA or miRNA backbone is in a range of about 0.1-100 or about 1-5, or said ratio is about 2.

3. The complex of claim 1 , wherein said quaternized polysaccharide is quaternized starch.

4. The complex of claim 3 , wherein the molecular weight of said starch is in a range selected from the group consisting of about 10 3 to about 10 8 daltons, about 10 4 to about 10 5 daltons and about 10 4 to 5×10 4 daltons, or said molecular weight is about 26,500 daltons.

5. The complex of claim 4 , wherein said starch is selected from the group consisting of rice starch, corn starch, potato starch, and potato soluble starch.

6. A pharmaceutical composition comprising the complex of claim 1 , and a pharmaceutically acceptable carrier.

7. The complex of claim 1 , wherein said quaternized polysaccharide is quaternized to its full capacity.

8. The complex of claim 7 , wherein said quaternized polysaccharide is quaternized starch having at least 3.5-4% nitrogen per monomeric unit, by weight.

9. A method for delivering a siRNA or miRNA to a target cell by administration of said siRNA or miRNA complexed with a quaternized polysaccharide, said polysaccharide being selected from the group consisting of starch, amylose, amylopectin, galactan and dextrin.

10. The method of claim 9 , further comprising applying ultrasound to a subject prior to, at the same time, and/or following administering said siRNA or miRNA complexed with the quaternized polysaccharide.

11. The method of claim 9 , wherein said quaternized polysaccharide is quaternized starch.

12. A method for treatment of ovarian cancer in a subject in need thereof, comprising administering to said subject a complex comprising siRNA or miRNA targeting the gene ABCB1 complexed with quaternized starch, wherein said ovarian cancer is amenable to treatment with said siRNA or miRNA.

Assignees

• B G Negev Tech And Applications Ltd
• Ramot At Tel-Aviv Univ Ltd

Inventors

• Kost Joseph
• Goldbart Riki
• Traitel Tamar
• Lewis Amar Eliz
• Lifshiz Rinat
• Peer Dan

Classifications

• C12N15/111 Primary

  General methods applicable to biologically active non-coding nucleic acids · CPC title

• A61K47/4823 Primary

  Human Necessities · mapped topic

• C12N2320/32

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

• A61K41/0047

  Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title