Antisense Oligonucleotides Targeting TNFR2 mRNA

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Solution Overview

Problem

Current methods for modulating the expression and function of TNFR2 polynucleotides are limited in their ability to specifically target and regulate the activity of TNFR2, leading to incomplete or inefficient therapeutic outcomes in diseases associated with TNFR2.

Innovation Solution

The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to the reverse complement of TNFR2 polynucleotides, which are administered to patient cells or tissues to modulate the expression and function of TNFR2, either by up-regulating or down-regulating its activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current methods for modulating TNFR2 expression are used, then therapeutic treatment is provided, but the ability to specifically target and regulate TNFR2 activity is limited resulting in incomplete therapeutic outcomes

Engineering Contradiction:
Improvetherapeutic outcome completenessVSAvoidTNFR2 targeting specificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent uses antisense oligonucleotides as intermediary molecules that specifically bind to TNFR2 mRNA through complementary base pairing. This intermediary approach allows precise targeting of TNFR2 expression without directly interacting with the protein itself, thereby improving both specificity and therapeutic completeness by blocking translation at the mRNA level

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces traditional protein-targeting mechanisms (mechanical/physical interaction with TNFR2 protein) with a molecular recognition system based on nucleic acid hybridization. The antisense oligonucleotides use sequence-specific binding to target TNFR2 mRNA, substituting direct protein interaction with a more precise nucleic acid-based recognition system that enhances targeting accuracy and therapeutic efficacy

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If antisense oligonucleotides are used to target TNFR2, then precise modulation of TNFR2 expression is achieved, but the complexity of the treatment approach increases

Engineering Contradiction:
ImproveTNFR2 modulation precisionVSAvoidtreatment approach complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex task of TNFR2 modulation into discrete oligonucleotide sequences of specific lengths (5-30 nucleotides) with defined sequence identity requirements (at least 50% to reverse complement). This segmentation allows the complex therapeutic goal to be achieved through standardized, modular oligonucleotide units that can be systematically designed and applied

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent establishes specific parameter thresholds for oligonucleotide design including length (5-30 nucleotides), sequence identity (at least 50% to reverse complement of TNFR2), and target region (nucleotides 1-413 of SEQ ID NO: 2 or 3). These parameter specifications simplify the complexity by providing clear design criteria that guide oligonucleotide selection and reduce variability in treatment approaches

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach effectively targets TNFR2, allowing for precise modulation of its expression and function, thereby providing a therapeutic benefit in treating diseases associated with TNFR2, such as cancer, autoimmune diseases, and inflammatory conditions.

Implementation Method 1

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

Methodology Applied
Scientific EffectDNA-RNA hybridization:

Data Source

PatentUS8859515B2Treatment of tumor necrosis factor receptor 2 (TNFR2) related diseases by inhibition of natural antisense transcript to TNFR2
Publication Date: 2014.10.14 CURNA INC
  • US8859515B2 patent drawing

AI summary

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Tumor Necrosis Factor Receptor 2 (TNFR2), in particular, by targeting natural antisense polynucleotides of Tumor Necrosis Factor Receptor 2 (TNFR2). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of TNFR2.