Antisense Oligonucleotides Targeting MicroRNA for Atherosclerosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for treating atherosclerosis are invasive, costly, and associated with significant post-operative risks, and there is a need for improved approaches to manage vascular conditions, particularly in regions exposed to disturbed blood flow which promotes atherogenesis.
Innovation Solution
The use of antisense nucleobase polymers and RNA interference therapeutic compositions that target specific microRNAs, such as miR-712, miR-205, and miR-663, to inhibit their activity, thereby increasing the expression of tissue inhibitor of metalloproteinase-3 (TIMP3) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK), which helps in preventing endothelial dysfunction and atherosclerosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If surgical procedures such as carotid endarterectomy are used to treat atherosclerosis, then stenosis in the common carotid artery can be corrected, but the procedures are expensive and associated with significant post-operative risks including heart attack, stroke, and death
Solution Approach 1:
The patent replaces mechanical surgical intervention (carotid endarterectomy) with a molecular/biochemical approach using antisense nucleobase polymers and RNA interference compositions. These molecular agents specifically target and inhibit the expression of pro-atherogenic genes, thereby treating atherosclerosis through genetic regulation rather than physical surgery, eliminating the need for invasive procedures and their associated risks
Solution Approach 2:
The patent introduces antisense nucleobase polymers and RNA interference compositions as intermediary molecules that mediate the treatment of atherosclerosis. These molecules act as intermediaries between the therapeutic goal and the target genes, specifically binding to and inhibiting pro-atherogenic microRNAs (such as miR-21, miR-133b, miR-378, and miR-205), thereby preventing their harmful effects without requiring direct surgical intervention
2Reliability
If disturbed blood flow conditions are present in arterial regions, then atherogenesis is promoted through alterations in gene expression, but there is currently no targeted approach to counteract this specific mechanism
Solution Approach 1:
The patent applies local quality by designing antisense nucleobase polymers and RNA interference compositions with specific sequence complementarity to pro-atherogenic microRNAs. These molecules are engineered to selectively bind only to their target microRNAs (such as miR-21, miR-133b, miR-378, miR-205) that are upregulated in disturbed flow conditions, thereby providing targeted inhibition of the specific molecular pathways driving atherogenesis in affected arterial regions
Solution Approach 2:
The patent utilizes parameter changes by modifying the expression levels of specific microRNAs through antisense and RNA interference mechanisms. The compositions are designed to specifically reduce the concentration and activity of pro-atherogenic microRNAs in arterial endothelial cells exposed to disturbed flow, thereby reversing the gene expression alterations that promote atherogenesis and restoring a more normal physiological state
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 reduces endothelial dysfunction and atherosclerosis by inhibiting miR-712 and its family members, leading to decreased metalloproteinase activity and reduced plaque formation, as demonstrated in various murine models, offering a less invasive and more effective treatment paradigm.
Implementation Method 1
The use of antisense nucleobase polymers and RNA interference therapeutic compositions that target specific microRNAs, such as miR-712, miR-205, and miR-663, to inhibit their activity
Implementation Method 2
compositions comprising isolated nucleobase polymers that binds or hybridizes any miRNA disclosed herein
Data Source
AI summary
This disclosure relates to methods and compositions for managing vascular conditions by targeting microRNA. In certain embodiments, the disclosure relates to antisense, RNA interference, and blocking oligonucleotide therapeutic compositions and uses related thereto.