Antisense Oligonucleotides Targeting IQGAP Natural Antisense Transcripts
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Solution Overview
Problem
Current methods for modulating the expression and function of IQGAP polynucleotides lack specificity and efficiency, particularly in targeting natural antisense transcripts and variants, which are essential for treating associated diseases.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to a reverse complement of IQGAP polynucleotides, administered via subcutaneous, intramuscular, or intravenous routes, to inhibit natural antisense transcripts and modulate IQGAP expression, incorporating modified nucleotides and delivery via liposomes or carrier molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to modulate IQGAP expression, then treatment can be provided, but specificity and efficiency are insufficient
Solution Approach 1:
The patent segments the therapeutic approach by specifically designing oligonucleotides that target only the natural antisense transcript of IQGAP, separating this specific target from other potential RNA molecules. This segmentation enables precise modulation of IQGAP expression without affecting other genes, thereby improving both treatment efficacy and specificity simultaneously
Solution Approach 2:
The patent introduces antisense oligonucleotides as intermediary molecules that bind specifically to the natural antisense transcript of IQGAP. These oligonucleotides act as mediators between the therapeutic intervention and the target gene, enabling controlled up-regulation of IQGAP expression with high specificity. The intermediaries (oligonucleotides) provide the mechanism for achieving both reliable treatment and precise targeting
2Measurement precision
If antisense oligonucleotides are designed with high sequence complementarity to target natural antisense transcripts, then specificity is improved, but complexity of design and manufacturing increases
Solution Approach 1:
The patent applies parameter changes by establishing specific design criteria for the oligonucleotides, including minimum sequence identity thresholds (at least 50%, preferably at least 75%) and specific length ranges (5-30 nucleotides). These parameter specifications simplify the design process by providing clear guidelines while ensuring high specificity for targeting natural antisense transcripts of IQGAP and its variants
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 IQGAP expression in patient cells, offering a therapeutic option for diseases related to IQGAP dysfunction by specifically targeting IQGAP polynucleotides with high sequence complementarity, enhancing treatment efficacy and specificity.
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
Implementation Method 2
Antisense DNA has the added feature that DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H, an activity that is present in most cell types
Data Source
Figure 1
AI summary
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of 'IQ motif containing GTPase activating protein' (IQGAP), in particular, by targeting natural antisense polynucleotides of 'IQ motif containing GTPase activating protein' (IQGAP). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of IQGAP.