Heparan Sulphate HS7 for VEGF Stabilization
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Solution Overview
Problem
Current VEGF therapies for ischemic heart and vascular diseases are limited by the instability of VEGF in physiological environments, requiring high doses that cause side effects and are costly, with heparin-based approaches being unsuitable due to anti-coagulant effects and non-specific binding to growth factors.
Innovation Solution
Development of heparan sulphate HS7 with high affinity for VEGF, isolated through a method involving polypeptide-glycosaminoglycan complexes, which can bind VEGF with low dissociation constant, promoting angiogenesis without the adverse effects of heparin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If VEGF is administered at high doses to achieve therapeutic concentrations, then angiogenic activity is improved, but side effects and cost increase
Solution Approach 1:
The patent uses heparan sulphate HS7 as an intermediary molecule that binds to VEGF and delivers it to ischemic tissues. This mediator approach allows VEGF to be administered at lower doses while achieving therapeutic effects through targeted delivery and sustained release, thereby reducing side effects associated with high-dose VEGF administration
Solution Approach 2:
The patent employs polymer-based biomaterials pre-loaded with VEGF and HS7 that are implanted at the ischemic site. This preliminary action ensures sustained release of VEGF over time, maintaining therapeutic concentrations without requiring high initial doses, thus reducing side effects while achieving reliable angiogenic activity
2Stability of the object's composition
If heparin is used to bind VEGF, then VEGF stability is improved, but anti-coagulant effects and non-specific binding occur
Solution Approach 1:
The patent isolates and uses a specific heparan sulphate species (HS7) with particular structural characteristics that provide VEGF binding capability without the anti-coagulant effects of heparin. This local quality approach selects only the beneficial properties (VEGF binding and stabilization) while eliminating the harmful properties (anti-coagulant activity) through precise molecular selection
Solution Approach 2:
The patent changes the chemical parameters of the heparin molecule by using heparan sulphate instead, which has different sulfation patterns and structural properties. This parameter change allows VEGF binding and stabilization while eliminating anti-coagulant effects, as HS7 binds VEGF with high affinity but does not activate anticoagulant pathways
3Reliability
If soluble VEGF protein is used, then pro-angiogenic effects are achieved, but instability and rapid degradation occur
Solution Approach 1:
The patent creates composite structures where VEGF is associated with heparan sulphate HS7 and polymer-based biomaterials. This composite approach provides structural stability to the otherwise unstable soluble VEGF protein, protecting it from degradation while maintaining its pro-angiogenic activity through the stabilizing influence of the HS7-polymer complex
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
HS7 effectively stimulates blood vessel growth, reduces VEGF dosage needs, and provides sustained VEGF activity, enhancing angiogenesis while avoiding heparin's side effects and non-specific binding issues.
Implementation Method 1
HS7 is capable of binding SEQ ID NO:1, optionally with a KD of less than 100 μM
Data Source
AI summary
Heparan sulphate HS7 is disclosed, together with the use of HS7 in the growth and/or development and/or regeneration of tissue.