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Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene

a tumor suppressor gene and gene technology, applied in the direction of antibacterial agents, sugar derivatives, material analysis, etc., can solve the problems of interfering with rna splicing, transcription, translation, replication,

Inactive Publication Date: 2011-12-01
CURNA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]Another embodiment provides a method of modulating function and / or expression of an Tumor Suppressor gene polynucleotide in patient cells or tissues in vivo or in vitro comprising contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to a reverse complement of the an antisense of the Tumor Suppressor gene polynucleotide; thereby modulating function and / or expression of the Tumor Suppressor gene polynucleotide in patient cells or tissues in vivo or in vitro.
[0009]Another embodiment provides a method of modulating function and / or expression of an Tumor Suppressor gene polynucleotide in patient cells or tissues in vivo or in vitro comprising contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to an Tumor Suppressor gene antisense polynucleotide; thereby modulating function and / or expression of the Tumor Suppressor gene polynucleotide in patient cells or tissues in vivo or in vitro.
[0050]An embodiment of the invention provides a method of preventing or treating a disease associated with at least one Tumor Suppressor gene polynucleotide and / or at least one encoded product thereof, comprising administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antisense sequence of said at least one Tumor Suppressor gene polynucleotide and modulates expression of said at least one Tumor Suppressor gene polynucleotide; thereby preventing or treating the disease associated with the at least one Tumor Suppressor gene polynucleotide and / or at least one encoded product thereof.

Problems solved by technology

Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA, thereby interfering with RNA splicing, transcription, translation, and replication.

Method used

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  • Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
  • Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
  • Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene

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example 1

Design of Antisense Oligonucleotides Specific for a Nucleic Acid Molecule Antisense to and / or Sense Strand of Tumor Suppressor Gene Polynucleotide

[0286]As indicated above the term “oligonucleotide specific for” or “oligonucleotide targets” refers to an oligonucleotide having a sequence (i) capable of forming a stable complex with a portion of the targeted gene, or (ii) capable of forming a stable duplex with a portion of an mRNA transcript of the targeted gene.

[0287]Selection of appropriate oligonucleotides is facilitated by using computer programs that automatically align nucleic acid sequences and indicate regions of identity or homology. Such programs are used to compare nucleic acid sequences obtained, for example, by searching databases such as GenBank or by sequencing PCR products. Comparison of nucleic acid sequences from a range of species allows the selection of nucleic acid sequences that display an appropriate degree of identity between species. In the case of genes that ...

example 2

Modulation of Tumor Suppressor Gene Oligonucleotide Gene Expression Treatment of HEPG2 Cells with Antisense Oligonucleotides

[0295]HepG2 cells from ATCC (cat#HB-8065) were grown in growth media (MEM / EBSS (Hyclone cat #SH30024, or Mediatech cat #MT-10-010-CV) +10% FBS (Mediatech cat#MT35-011-CV)+ penicillin / streptomycin (Mediatech cat#MT30-002-CI)) at 37° C. and 5% CO2. One day before the experiment the cells were replated at the density of 1.5×105 / ml into 6 well plates and incubated at 37° C. and 5% CO2. On the day of the experiment the media in the 6 well plates was changed to fresh growth media. All antisense oligonucleotides were diluted to the concentration of 20 μM. Two μl of this solution was incubated with 400 μl of Opti-MEM media (Gibco cat#31985-070) and 4 μl of Lipofectamine 2000 (Invitrogen cat#11668019) at room temperature for 20 min and applied to each well of the 6 well plates with HepG2 cells. Similar mixture including 2 μl of water instead of the oligonucleotide solut...

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Abstract

The present invention relates to antisense oligonucleotides that modulate the expression of and / or function of Tumor Suppressor genes, in particular, by targeting natural antisense polynucleotides of Tumor Suppressor genes. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Tumor Suppressor genes.

Description

CROSS REFERENCE[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 119,973, filed Dec. 4, 2008, U.S. Provisional Application No. 61 / 157,249, filed Mar. 4, 2009, U.S. Provisional Application No. 61 / 166,381, filed Apr. 3, 2009, and U.S. Provisional Application No. 61 / 154,594, filed Feb. 23, 2009, which applications are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]Embodiments of the invention comprise oligonucleotides modulating expression and / or function of Tumor Suppressor genes and associated molecules.BACKGROUND[0003]DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. Hybridization is also central to a variety of technologies that either detect a particular nucleic acid or alter its expression. Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA, thereby interfering with RNA splicing, tran...

Claims

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Application Information

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IPC IPC(8): A61K31/7088C07H21/00G01N25/04A61K31/712A61K31/7125A61K31/7115A61K31/713C07H21/04A61P35/00A61P37/06A61P35/02A61P37/00A61P43/00A61P25/28A61P25/00A61P25/16A61P29/00A61P9/00A61P9/10A61P19/10A61P7/00A61P31/12A61P17/02A61P3/10A61P3/00A61P13/12A61P9/04C12N5/09
CPCA61K31/712C12N15/1135C12Q2600/158C12Q1/6886C12N2310/11A61P13/12A61P17/02A61P19/02A61P19/08A61P19/10A61P21/02A61P25/00A61P25/14A61P25/16A61P25/28A61P29/00A61P3/00A61P31/04A61P31/12A61P31/18A61P35/00A61P35/02A61P37/00A61P37/02A61P37/06A61P39/02A61P43/00A61P7/00A61P9/00A61P9/04A61P9/10A61P3/10A61K31/7088C12Q2600/178C12N15/1137C12N2310/315C12N2310/14C12Q1/68
Inventor COLLARD, JOSEPHSHERMAN, OLGA KHORKOVA
Owner CURNA INC
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