US 8,101,741 B2 · Modified siRNA molecules and uses thereof

Abstract

The present invention provides chemically modified siRNA molecules and methods of using such siRNA molecules to silence target gene expression. Advantageously, the modified siRNA of the present invention is less immunostimulatory than its corresponding unmodified siRNA sequence and retains RNAi activity against the target sequence. The present invention also provides nucleic acid-lipid particles comprising a modified siRNA, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing gene expression by administering a modified siRNA to a mammalian subject. Methods for identifying and/or modifying an siRNA having immunostimulatory properties are also provided.

Claims43

Dependent claims

A modified siRNA comprising a double-stranded region of 19 to 25 nucleotides in length, wherein from 20% to 30% of the nucleotides in the double-stranded region comprise 2′-O-methyl (2′OMe) nucleotides,

wherein the modified siRNA comprises 2′OMe nucleotides in both strands of the modified siRNA,
wherein the modified siRNA comprises at least one 2′OMe-guanosine nucleotide and at least one 2′OMe-uridine nucleotide in the double-stranded region,
wherein 2′OMe-guanosine nucleotides and 2′OMe-uridine nucleotides are the only modified nucleotides present in the double-stranded region,
wherein the modified siRNA is chemically synthesized,
wherein the modified siRNA is less immunostimulatory than a corresponding unmodified siRNA sequence, and
wherein the modified siRNA is capable of silencing expression of a target sequence.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application

11/592,756Filed 2 Nov 2006 · us provisional application

Priority

2 Nov 2005

Published

US 2007/0135372 A114 Jun 2007

Granted

24 Jan 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C12N 15/113
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: non-coding nucleic acids modulating the…
A61K 9/1272
Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers: comprising non-phosphatidyl surfactants as…
A61K 31/713
Compounds having three or more nucleosides or nucleotides: double-stranded nucleic acids or oligonucleotides
A61K 48/00
Medicinal preparations containing genetic material which is inserted into cells of the

Modified siRNA molecules and uses thereof

Life of this patent

Modified siRNA molecules and uses thereof

Life of this patent

Abstract

Claims43