Compositions and processes for inhibiting gene expression using polynucleotides

• US 20030224055A1
• Filed: 05/28/2003
• Published: 12/04/2003
• Est. Priority Date: 05/28/2002
• Status: Abandoned Application

• Current Assignee: Roche Madison Inc. (Arrowhead Pharmaceuticals, Inc.)
• Original Assignee: Roche Madison Inc. (Arrowhead Pharmaceuticals, Inc.)
• Inventors: Wakefield, Darren, Rozema, David B., Lewis, David L., Herweijer, Hans, Hagstrom, James E., Wolff, Jon A.
• Application Number:
  US10/446,252
• Publication Number:
  US 20030224055A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/6931 the material constituting the nanoparticle being a polymer
• CPC Class Codes: C12N 15/113 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 Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2310/3145 with the nitrogen in 3' or 5'-position
• CPC Class Codes: C12N 2310/3181 Peptide nucleic acid, PNA
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring

Abstract

Compositions are provided for delivery of polynucleotides to cells for the purpose of inhibiting gene expression. Antisense polynucleotide-containing complexes are described. The salt and serum stability and small size of the complexes permits delivery to cells in vitro and in vivo.

Claims

1. A composition for delivering an antisense oligonucleotide to a cell in vivo comprising:

an antisense oligonucleotide, a polycation, and a polyanion wherein the oligonucleotide, polycation and polyanion associate to from ζ

-negative complex.

2. The composition of claim 1 wherein the polycation consists of a vinyl-amine based polymer.

3. The composition of claim 2 wherein the vinyl-amine based polymer consists of polyethyleneimine.

4. The composition of claim 3 wherein the polyethyleneimine consists of branched polyethyleneimine.

5. The composition of claim 2 wherein the vinyl-amine based polymer consists of polyallylamine.

6. The process of claim 1 wherein the polyanion consists of a poly(amino acid) polymer.

7. The process of claim 6 wherein the poly(amino acid) based polymer consists of succinylated poly-L-lysine.

8. The process of claim 1 wherein the polyanion consists of a poly(maleic anhydride) based polyanion.

9. The composition of claim 8 wherein the polyanion consists of a histamine containing poly(maleic anhydride) based polyanion.

10. The composition of claim 9 wherein the histamine containing poly(maleic anhydride) based polyanion consists of MC307.

11. The composition of claim 1 wherein the antisense polynucleotide consists of a phosphorodiamidate morpholino oligomer.

12. The composition of claim 11 wherein the phosphorodiamidate morpholino oligomer consists of a phosphorodiamidate morpholino oligomer hybridized to a oligodeoxynucleotide

13. The composition of claim 1 wherein the antisense polynucleotide consists of a peptide nucleic acid.

14. The composition of claim 1 wherein the cell consists of a mammalian liver cell.

15. The process of claim 14 wherein the liver cell consists of a hepatocyte.