Antisense Oligonucleotide Modulation of Tumor Suppressor Gene Expression
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Solution Overview
Problem
Current methods for modulating Tumor Suppressor gene expression are limited in effectively targeting and regulating the function of these genes, particularly in vivo or in vitro, with existing antisense oligonucleotides facing challenges in specificity and efficacy.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to reverse complements of Tumor Suppressor gene sequences, administered via various routes, including subcutaneously, intramuscularly, or intravenously, to modulate gene expression by binding to sense and antisense sequences, utilizing modified nucleotides and internucleotide linkages such as phosphorothioate and locked nucleic acids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antisense oligonucleotides are used to target Tumor Suppressor genes, then gene expression modulation is achieved, but specificity and efficacy are insufficient
Solution Approach 1:
The patent applies local quality by designing antisense oligonucleotides with specific chemical modifications (phosphorothioate linkages, locked nucleic acids) at specific positions to achieve localized enhancement of binding affinity and stability. This allows the oligonucleotide to selectively target particular regions of the Tumor Suppressor gene transcript, improving specificity without requiring complex overall structural modifications.
Solution Approach 2:
The patent employs parameter changes by systematically varying the chemical structure of the oligonucleotide backbone and modifying nucleotide properties (such as incorporating phosphorothioate instead of phosphodiester linkages, or using locked nucleic acids). These parameter modifications optimize the oligonucleotide's stability, cell penetration, and binding characteristics, thereby enhancing efficacy while managing complexity through controlled structural variation.
2Reliability
If antisense oligonucleotides are administered to modulate Tumor Suppressor gene expression, then therapeutic effect is achieved, but delivery challenges remain
Solution Approach 1:
The patent utilizes intermediary carriers or conjugates to facilitate the delivery of antisense oligonucleotides to target cells. These intermediaries can be cellular uptake mechanisms, endosomal escape vectors, or cellular transport proteins that mediate the delivery process. By incorporating such intermediary elements, the patent overcomes delivery barriers and improves the ease of administration while maintaining therapeutic efficacy.
Solution Approach 2:
The patent applies self-service principles by designing oligonucleotides with inherent properties that enable their own delivery and positioning within cells. This may include utilizing cellular endocytic pathways, membrane penetration capabilities, or intracellular trafficking mechanisms that the oligonucleotide exploits autonomously. Such self-service delivery reduces the need for complex external delivery systems, improving ease of administration.
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 up-regulates or down-regulates Tumor Suppressor gene expression, as demonstrated by increased mRNA levels in cell treatments, providing a therapeutic means to prevent or treat associated diseases.
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.
Implementation Method 2
DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H, an activity that is present in most cell types.
Data Source
AI summary
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.