Dual-Target siRNA Composition for Cancer Treatment
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Solution Overview
Problem
Current treatments for colorectal, gastric, and prostate cancers are limited, with no effective dual-targeted therapies available, and existing nucleic acid drugs face challenges such as easy degradation, interferon response, and poor penetration, which hinder their application in cancer treatment.
Innovation Solution
A dual-target RNA interference-based pharmaceutical composition that inhibits MyD88 and TGF-β1 gene expression using siRNA or miRNA molecules, combined with a pharmaceutically acceptable carrier like a histidine-lysine polymer, to effectively target tumor cells and inhibit cancer growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional chemotherapy and targeted therapy are used for colorectal, gastric, and prostate cancer, then tumor growth can be inhibited to some extent, but treatment options are limited and prognosis remains poor for advanced stages
Solution Approach 1:
The patent segments the treatment approach by targeting two distinct pathways (TGF-β1 and MyD88) simultaneously through separate siRNA molecules. This dual-targeting strategy divides the complex cancer treatment problem into two manageable genetic targets, allowing for more versatile treatment options while addressing multiple aspects of tumor progression including metastasis and immune evasion
Solution Approach 2:
The patent employs a composite delivery system combining cationic liposomes with histidine-lysine polymer to deliver both TGF-β1 siRNA and MyD88 siRNA. This composite material integrates multiple functional components (lipid bilayer for membrane fusion, polymeric component for stability and targeting) to overcome the limitations of conventional single-target therapies and improve drug delivery efficiency
2Object-affected harmful factors
If nucleic acid drugs (siRNA/miRNA) are used to target cancer genes, then specific gene expression can be inhibited, but the drugs face challenges of easy degradation, interferon response, and poor penetration
Solution Approach 1:
The patent introduces cationic liposomes as intermediary carriers to protect siRNA molecules from degradation by nucleases in the bloodstream. The liposomal membrane acts as a protective barrier, allowing the nucleic acid drugs to reach target cells intact while reducing immunogenicity and preventing premature degradation
Solution Approach 2:
The patent modifies the chemical parameters of the delivery system by incorporating histidine-lysine polymer with specific molecular weight and charge characteristics. This parameter optimization enhances the complex's stability, improves cellular uptake efficiency, and reduces interferon response while maintaining effective gene silencing capability
3Adaptability or versatility
If dual-targeted therapy is developed to improve treatment versatility, then more cancer pathways can be addressed, but device and formulation complexity increases
Solution Approach 1:
The patent merges two separate siRNA targeting molecules (TGF-β1 siRNA and MyD88 siRNA) into a single liposomal formulation. This combining strategy allows simultaneous delivery of multiple therapeutic agents through one administration route, achieving dual-targeted therapy while simplifying the treatment protocol compared to separate administrations
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 composition significantly inhibits the growth of colorectal, gastric, and prostate cancer cells in vivo, demonstrating potential as a new treatment option with improved safety and efficacy compared to conventional therapies.
Implementation Method 1
A dual-target RNA interference-based pharmaceutical composition that inhibits MyD88 and TGF-β1 gene expression using siRNA or miRNA molecules
Implementation Method 2
combined with a pharmaceutically acceptable carrier like a histidine-lysine polymer, to effectively target tumor cells
Data Source
AI summary
Provided herein are nucleic acid interference pharmaceutical compositions, and drugs for treating colorectal cancer, gastric cancer and prostate cancer. For two targets (TGF-β1 and MyD88) related to tumor microenvironment and tumor metastasis in colorectal cancer, gastric cancer, and prostate cancer, an MyD88/TGF-β1 dual-target nucleic acid interference pharmaceutical composition (composition number STP500) is designed and selected, which includes an active ingredient and a pharmaceutically acceptable carrier. The active ingredient includes a first active ingredient capable of inhibiting and silencing the expression of the MyD88 gene and a second active ingredient capable of inhibiting and silencing the expression of TGF-β1 gene. In vivo and in vitro experiments show that the MyD88/TGF-β1 dual-target nucleic acid interference pharmaceutical composition can effectively inhibit the growth of tumor cells in colorectal cancer, gastric cancer, and prostate cancer, and has application for the treatment of colorectal cancer, gastric cancer, and prostate cancer.