Oxocarbonamide peptide nucleic acids and methods of using same

Active Publication Date: 2012-11-29
LUMINEX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0080]In certain aspects, the association constant (Ka) of the oxocarbonamide peptide nucleic acid toward a complementary target molecule is higher than the association constant of the complementary strands of the double stranded target molecule. In some embodiments, the melting temperature of a duplex between the oxocarbonamide peptide nucleic acid and a complementary target molecule is higher than the melting temperature of the complementary strands of the double stranded target molecule.
[0081]In one aspect, the present invention provides pharmaceutical composition comprising an oxocarbonamide peptide nucleic acid for treatment of a disease curable by an antisense technology. In one embodiment, the invention provides a method for inhibiting the expression of a target nucleic acid in a cell. The method comprises introducing into the cell a oxocarbonamide peptide nucleic acid of the invention in an amount sufficient to specifically attenuate expression of the target nucleic acid. The introduced oxocarbonamide peptide nucleic acid has a nucleotide sequence that is complementary to a region of the target nucleic acid sequence. In another aspect, the invention provides a method for preventing, stabilizing, or treating a disease, disorder, or condition associated with a target nucleic acid in a mammal. This method comprises introducing into the mammal oxocarbo

Problems solved by technology

Disadvantages of all the gel-based assays (Northern blotting, primer extension, RNase protection assays etc.) for monitoring miRNA expression include low throughput and poor sensitivity.
Consequently, a large amount of total RNA per sample is required for gel-based methods, which is not feasible when the cell or tissue source is limited.
Although microarrays can provide high throughput, the disadvantages of DNA-based oligonucleotide arrays may include: the requirement of high concentrations of labeled input target RNA for efficient hybridization and signal generation, low sensitivity for rare and low-abundant miRNAs, and the necessity for post-array validation using more sensitive assays.
However, this method is cumbersome for routine miRNA expression profiling, since it involves gel isolation of small RNAs and ligation to linker oligonucleotides.
The disadvantage of this method, however, is that it only allows quantification of the precursor miRNAs, which does not necessarily reflect the expression levels of mature miRNAs.

Method used

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  • Oxocarbonamide peptide nucleic acids and methods of using same
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Embodiment Construction

A. The Present Invention

[0098]The present invention provides novel oxocarbon acid incorporated peptide nucleic acids (OxoPNAs) that provide increased stability, sensitivity, and specificity as compared to their natural DNA and RNA counterparts. The OxoPNAs of the invention generally comprise nucleobases linked to an oxocarbon acid amide incorporated peptide backbone. The nucleobases may include any of the four main naturally occurring DNA bases (i.e., thymine, cytosine, adenine, or guanine) or other naturally occurring nucleobases (e.g., inosine, uracil, 5-methylcytosine, or thiouracil) or artificial bases (e.g., bromothymine, azaadenines, or azaguanines, etc.) attached to a peptide backbone through a suitable linker. The oxocarbon acid may be squaric acid, deltic acid, croconic acid, rhodizonic acid, or their corresponding thioxocarbon acids.

[0099]The present invention also provides a variety of methods employing the OxoPNAs of the present invention. As described herein, the oligon...

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Abstract

The present invention concerns oxocarbonamide peptide nucleic acids (OxoPNAs). OxoPNAs provide increased stability, sensitivity, and specificity as compared to their natural DNA and RNA counterparts. The OxoPNA molecules of the present invention may be employed in a wide range of applications, particularly in applications involving hybridization. For example, OxoPNA probes may be employed for the detection and functional analysis of nucleic acid molecules, including miRNAs and other non-coding RNAs.

Description

[0001]This application claims priority to U.S. Application No. 60 / 868,514, filed on Dec. 4, 2006, the entire disclosure of which is incorporated by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates generally to nucleic acid probes useful in the detection and analysis of target nucleic acid sequences. More particularly, the present invention concerns nucleic acid probes wherein naturally occurring nucleobases or other nucleobase-binding moieties are covalently bound to an oxocarbonamide containing peptide backbone. In certain aspects, the present invention concerns methods employing nucleic acid probes in the detection and analysis of target nucleic acid sequences including, for example, mRNAs, miRNAs, and siRNAs.[0004]2. Description of Related Art[0005]A large number of small, non-coding RNAs have been identified and designated as microRNAs (miRNAs) (Ke et al., 2003). miRNAs have been shown to regulate gene expression at many lev...

Claims

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Application Information

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IPC IPC(8): C07K2/00C40B30/04C12Q1/68G01N21/64
CPCC07K14/003
InventorLUGADE, ANANDA G.JACOBSON, JAMES W.
OwnerLUMINEX