dsRNA Agents Targeting Coagulation Factor X mRNA
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Solution Overview
Problem
Current treatments for thrombosis are non-selective, leading to excessive bleeding due to the lack of specificity, necessitating a more effective approach to manage coagulation Factor X activity.
Innovation Solution
Development of dsRNA agents that mediate RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts for coagulation Factor X, specifically designed to inhibit its expression by targeting its mRNA with complementary sequences, thereby reducing its activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-selective anti-coagulant therapy is used to treat thrombosis, then thrombosis is treated, but excessive bleeding occurs due to lack of specificity
Solution Approach 1:
The patent introduces dsRNA molecules as intermediaries that specifically bind to and degrade Factor X mRNA transcripts. This mediator approach allows selective inhibition of Factor X expression without affecting other coagulation factors, thereby treating thrombosis while avoiding excessive bleeding associated with non-selective therapies
Solution Approach 2:
The invention applies local quality by designing dsRNA agents with specific nucleotide sequences that are complementary only to Factor X mRNA. This sequence specificity ensures that the therapeutic effect is localized to Factor X inhibition, leaving other coagulation pathways intact and avoiding systemic bleeding risks
2Object-affected harmful factors
If Factor X activity is inhibited to prevent thrombosis, then thrombosis risk is reduced, but coagulation function may be compromised
Solution Approach 1:
The patent employs partial action by using dsRNA agents that reduce Factor X expression to a therapeutic level rather than complete elimination. This partial inhibition is sufficient to prevent thrombosis while maintaining adequate coagulation function for hemostasis, avoiding over-suppression of the coagulation system
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 agents effectively inhibit coagulation Factor X expression, reducing the risk of thrombosis-related disorders by specifically targeting and degrading its mRNA, thereby decreasing the formation of excess clots and associated bleeding risks.
Implementation Method 1
dsRNA agents that mediate RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts for coagulation Factor X
Implementation Method 2
RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts
Implementation Method 3
the sense strand comprises at least 15 contiguous nucleotides differing by no more than 0, 1, 2, or 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 1, 2, or 3 nucleotides from the nucleotide sequence of SEQ ID NO:8
Data Source
AI summary
The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the Coagulation Factor X (F10) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an F10 gene and to methods of treating or preventing an F10-associated disease, e.g., a disorder associated with thrombosis, in a subject.