SERPINC1 dsRNA Composition for Hemophilia Bleeding Control
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Solution Overview
Problem
Current treatments for bleeding disorders like hemophilia, such as hemophilia A and B, are inadequate due to the development of antibodies against replacement clotting factors, necessitating the need for alternative therapies that can effectively inhibit Serpinc1 expression to control bleeding.
Innovation Solution
Development of stable pharmaceutical compositions comprising a double-stranded ribonucleic acid (dsRNA) agent that targets Serpinc1 gene expression, with specific nucleotide sequences and chemical modifications, suitable for subcutaneous administration, to inhibit Serpinc1 gene expression and improve stability, efficacy, and ease of administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If replacement clotting factors are administered to treat hemophilia, then bleeding control is improved, but antibody formation against the replacement factors occurs, rendering the treatment ineffective
Solution Approach 1:
The invention targets and silences the Serpinc1 gene, which produces antithrombin - a protein that naturally inhibits clotting. By reducing antithrombin levels through RNA interference, the patent converts the harmful effect (antibody formation against replacement factors) into a beneficial outcome (enhanced response to replacement clotting factors), as patients without functional antithrombin do not develop inhibitors against administered factors
Solution Approach 2:
The invention extracts and eliminates the problematic component (Serpinc1 gene expression) from the system. By using dsRNA to specifically target and silence the Serpinc1 gene, the patent removes the source of antithrombin production, thereby preventing antibody formation while preserving the ability to respond to replacement clotting factors
2Reliability
If dsRNA agents are used to inhibit Serpinc1 expression, then treatment efficacy is improved, but stability and ease of administration are compromised
Solution Approach 1:
The invention modifies the chemical parameters of the dsRNA agent by incorporating 2′-O-methyl modifications on specific nucleotides. This chemical modification enhances the stability of the dsRNA agent against degradation while maintaining its ability to inhibit Serpinc1 expression, thereby improving both efficacy and ease of administration through subcutaneous injection
Solution Approach 2:
The patent uses a lipid conjugate as an intermediary carrier that facilitates the delivery of the dsRNA agent to the liver. This lipid mediator enables subcutaneous administration by protecting the dsRNA from degradation in the bloodstream and facilitating cellular uptake, thereby improving ease of administration while maintaining treatment efficacy
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 dsRNA agent effectively inhibits Serpinc1 gene expression, providing a stable and durable treatment option for bleeding disorders, with improved stability and ease of administration, potentially reducing bleeding episodes in subjects.
Implementation Method 1
a double-stranded ribonucleic acid (dsRNA) agent that inhibits the expression of a Serpinc1 gene
Data Source
AI summary
The invention relates to pharmaceutical compositions comprising an iRNA agent, e.g., double stranded ribonucleic acid (dsRNA) agent and methods of using such compositions to treat a bleeding event in a subject having a hemophilia (e.g., with or without inhibitors).