Targeted Thrombolytic Polypeptide for Low-Bleeding Clot Dissolution
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Solution Overview
Problem
Existing thrombolytic agents cause severe bleeding side effects due to their non-specific action on both intravascular and hemostatic blood clots, complicating thrombosis treatment and interfering with wound healing.
Innovation Solution
A polypeptide with a thrombolytic domain and thrombo-recognition domain, characterized by specific amino acid sequences, specifically targets and dissolves intravascular thrombi without activating plasminogen to plasmin, thereby minimizing bleeding and preserving wound healing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional thrombolytic agents (tPA, urokinase, streptokinase) are used to dissolve intravascular thrombus, then thrombolytic effect is achieved, but severe bleeding side effects occur due to non-specific degradation of hemostatic blood clots
Solution Approach 1:
The thrombolytic agent is divided into two distinct functional domains: a thrombo-recognition domain (amino acid sequence SEQ ID NO: 3 or SEQ ID NO: 4) that specifically binds to intravascular thrombus, and a thrombolytic domain (amino acid sequence SEQ ID NO: 1 or SEQ ID NO: 2) that degrades fibrin. This segmentation enables the agent to first recognize and bind to the target thrombus before activating plasminogen, ensuring localized and specific thrombolysis while preserving hemostatic clots.
2Object-affected harmful factors
If anticoagulants and antiplatelet agents are used instead of thrombolytics, then bleeding side effects are avoided, but they cannot dissolve existing clots and interfere with wound healing
Solution Approach 1:
The thrombolytic agent acts as an intermediary that bridges the gap between anticoagulants and thrombolytics. Like anticoagulants, it does not cause systemic bleeding because it is highly specific. Like thrombolytics, it actively dissolves existing clots. The thrombo-recognition domain serves as the intermediary structure that provides specificity, enabling the agent to distinguish pathological thrombus from physiological hemostatic clots, thus achieving both clot dissolution and bleeding prevention.
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 polypeptide effectively treats thrombosis with 100% survival rate in animal models, reduces bleeding side effects, and maintains normal wound healing processes, demonstrating superior thrombolytic activity and specificity.
Implementation Method 1
These thrombolytic agents, i.e., tPA (alteplase, reteplase), urokinase, and streptokinase, all bind to plasminogen in the body and activate it into plasmin, the activated enzyme that breaks down the thrombus, resulting thrombolysis.
Implementation Method 2
A polypeptide with a thrombolytic domain and thrombo-recognition domain, characterized by specific amino acid sequences, specifically targets and dissolves intravascular thrombi
Data Source
AI summary
Provided is a thrombolytic agent for ‘intravascular thrombus’, and more particularly, to a thrombolytic agent having a thrombo-recognition domain and a thrombolytic domain. It also relates to a polypeptide for thrombolysis of an intravascular thrombus, a gene for that polypeptide, and a pharmaceutical composition containing the same. The polypeptide that recognizes ‘intravascular thrombus’ and dissolves thrombus of the present invention is characterized in that it consists of a thrombolytic domain comprising the amino acid sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2 and a thrombo-recognition domain comprising the amino acid sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 4. According to the present invention, the polypeptide for dissolving thrombus by recognizing ‘intravascular thrombus’ dissolves thrombus in the blood of a mammal without serious bleeding side effects has a preventive and therapeutic effect on thrombosis, thus preventing thrombosis and related diseases.