Fusion Peptide Thrombus Targeting and Dissolution
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Solution Overview
Problem
Current thrombolytic therapies, such as tissue plasminogen activator (tPA), have limitations including unspecific activation leading to systemic hemorrhages and require invasive procedures, necessitating a novel thrombolytic agent that specifically targets thrombus formation sites without causing life-threatening hemorrhages.
Innovation Solution
A fusion peptide comprising a clot-targeting peptide, a ferritin fragment, and microplasminogen or microplasmin, sequentially linked, which forms a cage protein that specifically targets and dissolves thrombi with minimal systemic inactivation by anti-plasmin, reducing bleeding side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tPA is administered systemically to dissolve thrombi, then thrombolytic activity is improved, but systemic hemorrhages occur due to unspecific activation of plasminogen
Solution Approach 1:
The invention creates a thrombus-specific thrombolytic agent by fusing the clot-targeting peptide (which confers specificity to thrombus sites) with microplasminogen (which provides thrombolytic function). This ensures that plasminogen activation occurs only at the thrombus location rather than systemically, thereby maintaining thrombolytic activity while preventing systemic hemorrhages through localized action
Solution Approach 2:
The invention uses a clot-targeting peptide as an intermediary that directs microplasminogen to the thrombus site. This intermediary component enables specific targeting of the thrombolytic agent to the clot, ensuring that plasminogen activation is confined to the thrombus and not activated in normal tissues, thus resolving the contradiction between effective thrombolysis and prevention of systemic bleeding
2Reliability
If plasmin is administered to dissolve thrombi, then direct thrombus dissolution is achieved, but invasive catheter procedures are required for local administration
Solution Approach 1:
The fusion peptide is designed to autonomously target and dissolve thrombi without requiring invasive delivery methods. The clot-targeting peptide component enables the molecule to self-direct to the thrombus site through specific binding, and the microplasminogen component automatically activates to dissolve the clot upon reaching the target, eliminating the need for catheter-based local administration
Solution Approach 2:
The invention extracts the essential functions of plasmin (thrombus dissolution) and combines them with a targeting moiety (clot-targeting peptide) in a single fusion molecule. This extracted and recombined functionality allows the thrombolytic agent to work autonomously in the circulation without requiring invasive delivery systems, thereby simplifying the treatment approach
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 fusion peptide effectively targets and dissolves thrombi with enhanced clot-binding affinity and thrombolytic activity, while minimizing systemic inactivation and bleeding risks, making it suitable for treating thrombotic diseases with fewer side effects.
Implementation Method 1
a clot-targeting peptide... sequentially linked
Implementation Method 2
The tPA converts plasminogen to plasmin, which degrades fibrin clots to restore the normal flow of blood
Data Source
AI summary
The present invention relates to: a fusion peptide comprising a thrombus-targeting peptide, ferritin fragment and a thrombolytic peptide; and a use thereof and, more specifically, to: a fusion peptide in which a thrombus-targeting peptide, ferritin fragment and a thrombolytic peptide are sequentially linked; a composition for preventing or treating thrombotic disorders, containing the same as an active ingredient; a method for treating thrombotic disorders; and a therapeutic use. According to the present invention, CLT-sFt-μPn DCNC as a novel plasmin-based thrombolytic nanocage has: an effect of targeting a site at which thrombus is present; a low sensitivity to inhibitors present in the circulatory system; pharmacological activity strongly destroying both arterial and venous thrombi; and no side effects of bleeding, and thus can be very useful in developing an agent for preventing or treating thrombotic disorders.