F5 dsRNA Composition for Selective Thrombosis Control
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Solution Overview
Problem
Current treatments for thrombosis lack specificity, leading to excessive bleeding due to non-selective anti-coagulant therapy.
Innovation Solution
Development of double-stranded ribonucleic acid (dsRNA) agents that target and inhibit the expression of coagulation Factor V (F5) through RNA-induced silencing complex (RISC)-mediated cleavage, using specific nucleotide sequences and modifications to reduce unregulated activation and clotting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-selective anti-coagulant therapy is used to treat thrombosis, then clotting is reduced, but excessive bleeding occurs due to lack of specificity
Solution Approach 1:
The patent applies local quality by designing dsRNA agents with specific nucleotide sequences that target only the F5 gene in specific tissues (such as liver), rather than systemically inhibiting coagulation. This localized gene silencing approach treats thrombosis at its source while preserving bleeding homeostasis in other tissues.
Solution Approach 2:
The patent uses an intermediary mechanism (RNA-induced silencing complex or RISC) to achieve selective gene inhibition. The dsRNA agents serve as intermediaries that guide the RISC complex to specifically degrade F5 mRNA, providing a controlled and selective way to reduce Factor V production without broad-spectrum anti-coagulant effects.
2Reliability
If F5 expression is inhibited to reduce clotting, then thrombosis is treated, but F5 is essential for coagulation function
Solution Approach 1:
The patent achieves local quality by restricting F5 gene silencing to specific tissues where it is most needed for thrombosis treatment (such as liver), while preserving F5 expression in other tissues where it is necessary for normal coagulation function. This spatial selectivity allows treatment without global coagulation deficiency.
Solution Approach 2:
The patent applies dynamics by using inducible and reversible gene silencing through dsRNA agents. The inhibition of F5 expression is dynamic rather than permanent, allowing the system to adapt F5 levels according to physiological needs while maintaining the ability to treat thrombosis when required.
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
Effectively inhibits F5 expression, reducing blood clot formation and associated disorders like thrombosis, with minimal bleeding risks, by administering dsRNA agents that target and degrade F5 mRNA.
Implementation Method 1
iRNA compositions which effect the RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts of a gene encoding coagulation Factor V (F5)
Implementation Method 2
the antisense 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:2
Data Source
AI summary
The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the Coagulation Factor V (F5) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an F5 gene and to methods of treating or preventing an F5-associated disease, e.g., a disorder associated with thrombosis, in a subject.