MULTI-TARGETING SHORT INTERFERING RNAs

Patent metadata

Field	Value
Publication number	US-2017004254-A1
Application number	US-201615273094-A
Country	US
Kind code	A1
Filing date	Sep 22, 2016
Priority date	Jan 29, 2007
Publication date	Jan 5, 2017
Grant date	—

Abstract

The present invention relates to novel short interfering RNA (siRNA) molecules that are multi-targeted. More specifically, the present invention relates to siRNA molecules that target two or more sequences. In one embodiment, multi-targeting siRNA molecules are designed to incorporate features of siRNA molecules and features of micro-RNA (miRNA) molecules. In another embodiment, multi-targeting siRNA molecules are designed so that each strand is directed to separate targets.

First claim

What is claimed is:

1 . A method for designing a multi-targeting RNA molecule comprising:
(a) inputting one mRNA and one 3′ UTR target sequence; (b) identifying all 19mer siRNA candidates that have perfect complementarity to the mRNA; (c) identifying effective cleavage target sites within the mRNA with an siRNA efficacy prediction algorithm; and (d) ordering the siRNA candidates based on predicted miRNA-like down-regulation.

2 . The method of claim 1 , wherein the predicted miRNA-like down-regulation is based on the number of and distance between miRNA-like target sites within the 3′ UTR.

3 . The method of claim 1 which further comprises (b′) identifying miRNA-like target sites within the 3′ UTR for each siRNA candidate and removing candidates that have no miRNA-like target sites.

4 . The method of claim 1 which further comprises (b′) identifying miRNA-like target sites within the 3′ UTR for each siRNA candidate and removing candidates that have no miRNA-like target sites.

5 . A multi-targeting RNA molecule that targets two different desired mRNA target sequences, wherein the siRNA comprises a first strand having a 5′ terminus and a 3′ terminus and a second strand having a 5′ terminus and a 3′ terminus, wherein the first strand is 19-30 nucleotides in length, wherein the second strand is 19-30 nucleotides in length, wherein the first strand is perfectly complementary to a first desired mRNA target sequence, wherein the second strand is perfectly complementary to a second and different desired mRNA target sequence, wherein the first strand and second strand are not completely complementary and wherein the first strand and the second strand hybridize to form a double stranded siRNA, wherein the double stranded siRNA is a single duplex.

6 . The multi-targeting RNA molecule of claim 5 , wherein the first strand results in cleavage of the first desired mRNA target sequence and the second strand results in cleavage of the second and different desired mRNA target sequence.

7 . A composition comprising a therapeutically effective amount of the multi-targeting RNA molecule of claim 5 and a pharmaceutically acceptable carrier.

Assignees

• Hope City

Inventors

• Rossi John J
• Snove Ola
• Ehsani Ali
• Saetrom Pal
• Vallazza Britta
• Zhang Jane
• Aagaard Lars

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title