Antisense Oligonucleotides Targeting PAR4 Natural Antisense Transcripts
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Solution Overview
Problem
Current methods for modulating the expression and function of PAR4 polynucleotides are limited in their ability to specifically target and regulate the natural antisense transcripts, leading to incomplete or inefficient modulation of gene expression.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to a reverse complement of a PAR4 polynucleotide sequence, which are administered to patient cells or tissues to modulate the expression and function of PAR4, either by up-regulating or down-regulating its activity, utilizing modified nucleotides and delivery methods such as liposomes or carrier molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional antisense oligonucleotides are used to target PAR4, then gene expression modulation is achieved, but the ability to specifically target natural antisense transcripts is insufficient
Solution Approach 1:
The invention divides the targeting strategy into two distinct segments: one oligonucleotide component targets the sense transcript while another component targets the natural antisense transcript. This segmentation allows each component to specifically bind its intended target without cross-interference, thereby achieving both high specificity for natural antisense transcripts and complete gene expression modulation through coordinated action on both transcript types.
2Manufacturing precision
If antisense oligonucleotides are designed with high sequence identity to reverse complement of PAR4, then specificity increases, but delivery efficiency and cellular uptake may be compromised
Solution Approach 1:
The invention introduces delivery vehicles such as liposomes, nanoparticles, or protein carriers as intermediaries that facilitate the transport of highly specific antisense oligonucleotides into patient cells. These intermediary delivery systems protect the oligonucleotides from degradation, enhance cellular uptake through endocytosis or membrane fusion, and enable the highly specific sequences to reach their intracellular targets effectively, thereby resolving the contradiction between sequence specificity and delivery efficiency.
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
The approach effectively increases PAR4 mRNA levels and induces apoptosis in various cell types, demonstrating significant modulation of PAR4 expression and function, as shown by real-time PCR and apoptosis increase data.
Implementation Method 1
DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. 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
AI summary
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of PAR4, in particular, by targeting natural antisense polynucleotides of PAR4. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of PAR4.