MARC1 RNAi Combination Therapy for Sustained Obesity Control
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Solution Overview
Problem
Existing obesity treatments, such as semaglutide, lead to significant weight regain and increased cardiometabolic risk factors upon discontinuation, and there is a need for safer and more effective therapeutic agents to manage obesity.
Innovation Solution
A pharmaceutical composition using an RNAi agent that specifically inhibits MARC1 expression, combined with a GLP-1 receptor agonist or GLP-1/GIP receptor dual agonist, to enhance weight management and maintain efficacy post-treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If semaglutide or other existing obesity treatments are used, then weight loss is achieved during treatment, but significant weight regain occurs and cardiometabolic risk factors increase upon discontinuation
Solution Approach 1:
The patent applies preliminary action by using RNAi to silence MARC1 gene expression before obesity fully develops or before weight regain can occur. The RNAi agent is administered to prevent the underlying genetic mechanism (MARC1-mediated mitochondrial function) that drives weight regain, thereby maintaining weight loss effects even after discontinuation of therapeutic agents.
Solution Approach 2:
The patent uses RNAi as an intermediary mechanism to target and silence MARC1 gene expression. This RNAi-mediated gene silencing acts as a mediator between the administered therapeutic agent and the mitochondrial function, providing sustained metabolic changes that persist after the agent is discontinued.
2Reliability
If RNAi agent targeting MARC1 is used to promote fat oxidation and increase basal metabolism, then sustained weight loss is achieved, but the complexity of the therapeutic regimen increases
Solution Approach 1:
The patent achieves multi-functionality by using a single RNAi agent that simultaneously promotes fat oxidation and increases basal metabolism through MARC1 gene silencing. This single therapeutic agent addresses multiple metabolic parameters related to obesity, simplifying the overall therapeutic approach while maintaining sustained weight loss effects.
3Reliability
If combination therapy with GLP-1 receptor agonist or GLP-1/GIP receptor dual agonist is used with RNAi agent, then weight management efficacy is enhanced, but the complexity of treatment increases
Solution Approach 1:
The patent merges two distinct therapeutic mechanisms: RNAi-mediated MARC1 gene silencing and GLP-1/GLP-1/GIP receptor agonism. This combination therapy integrates genomic-level intervention (RNAi) with receptor-level modulation (GLP-1 pathway), creating a multi-target approach that enhances weight management efficacy while addressing different aspects of obesity pathophysiology.
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 RNAi agent promotes fat oxidation and increases basal metabolism, providing sustained weight loss and reducing side effects when used with GLP-1 receptor agonists, maintaining weight loss effects even after drug discontinuation.
Implementation Method 1
treatment of a disease using the phenomenon of RNA interference has been attracting attention as a safer therapeutic agent for the treatment for a disease, since it targets mRNA and uses small interfering RNA (siRNA) to regulate gene expression at a translational level
Data Source
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AI summary
The present disclosure relates to an RNAi agent for preventing or treating obesity and combination therapy using the same. Specifically, the present disclosure relates an RNAi agent including an antisense strand having sequence complementarity to a MARC1 mRNA sequence and a sense strand having sequence complementarity to the antisense strand, and a pharmaceutical composition including the RNAi agent for preventing or treating obesity, and combination therapy of (i) the RNAi agent and (ii) GLP-1 receptor agonist or GLP-1/GIP receptor dual agonist.