RNA agents for GST-Pi gene modulation

Patent metadata

Field	Value
Publication number	US-10047110-B2
Application number	US-201514979567-A
Country	US
Kind code	B2
Filing date	Dec 28, 2015
Priority date	Dec 26, 2014
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

This invention provides compounds, compositions and methods for modulating the expression of human GST-π using RNA interference. The RNA interference molecules can be used in methods for preventing or treating diseases such as malignant tumor. A nucleic acid molecule can have a) a polynucleotide sense strand and a polynucleotide antisense strand; b) each strand of the molecule being from 15 to 30 nucleotides in length; c) a contiguous region of from 15 to 30 nucleotides of the antisense strand being complementary to a sequence of an mRNA encoding GST-π; and d) at least a portion of the sense strand can be complementary to at least a portion of the antisense strand, and the molecule has a duplex region of from 15 to 30 nucleotides in length.

First claim

What is claimed is:

1. A nucleic acid molecule, wherein:
the molecule has a polynucleotide sense strand and a polynucleotide antisense strand;
wherein a contiguous region of the antisense strand is complementary to a sequence of an mRNA encoding GST-π; and
wherein the antisense strand is UAGGGUCUCAAAAGGCUUCag (SEQ ID NO:1341), and the sense strand is GAAGCCUUUUGAGACCCUAtt (SEQ ID NO:1276); or wherein the antisense strand is ACAGCAGGGUCUCAAAAGGct (SEQ ID NO:1305), and the sense strand is CCUUUUGAGACCCUGCUGUtt (SEQ ID NO:1240)
wherein upper case letters refer to ribonucleotides and lower case letters refer to deoxyribonucleotides.

2. The nucleic acid molecule of claim 1 , wherein the polynucleotide sense strand and the polynucleotide antisense strand are connected as a single strand, and form a duplex region connected at one end by a loop.

3. The nucleic acid molecule of claim 1 , wherein the molecule is an RNAi molecule active for gene silencing.

4. The nucleic acid molecule of claim 1 , wherein the molecule is active for inhibiting expression of GST-π.

5. The nucleic acid molecule of claim 1 , wherein the molecule has an IC50 for knockdown of GST-π in A549 cells of less than 100 pM.

6. A composition comprising one or more nucleic acid molecules of claim 1 and a pharmaceutically acceptable carrier.

7. The composition of claim 6 , wherein the carrier is a lipid molecule or liposome.

8. A method for treating pancreatic cancer or lung cancer, the method comprising administering to a subject in need a composition of claim 6 .

9. The method of claim 8 , wherein the disease is pancreatic cancer.

10. The nucleic acid molecule of claim 1 , wherein at least one or more nucleotides in any strand is chemically modified.

Assignees

• Nitto Denko Corp

Inventors

• Minomi Kenjirou
• Takahashi Hirokazu
• Terada Erika
• Harborth Jens
• Zhang Jun
• Ahmadian Mohammad
• Ying Wenbin

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C12N2320/32

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

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• C12N2310/322

  2'-R Modification · CPC title

• A61K31/713 Primary

  Double-stranded nucleic acids or oligonucleotides · CPC title