Collagen-Binding Peptides and Conjugates for Damaged Cartilage
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Solution Overview
Problem
Existing therapies, such as mesenchymal stem cell (MSC) injections, struggle to effectively target and engraft in damaged cartilage, limiting their therapeutic efficacy in osteoarthritis and other collagen-related disorders.
Innovation Solution
Development of peptides comprising specific modules of the collagen binding domain (CBD) of matrix metalloproteinases (MMP-2 and MMP-9) with enhanced binding affinity for type I and type II collagen gelatin, enabling targeted delivery of therapeutic payloads to sites of collagen damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mesenchymal stem cells are injected into joints of osteoarthritis patients, then pain reduction is achieved, but engraftment into cartilage does not occur
Solution Approach 1:
The patent uses gelatin-binding peptides as intermediary molecules that bridge the gap between MSCs and damaged cartilage. These peptides are conjugated to MSC surfaces, enabling them to specifically bind to gelatin exposed at sites of collagen degradation in osteoarthritic cartilage, thereby achieving targeted delivery and engraftment
Solution Approach 2:
The patent modifies the surface properties of MSCs by conjugating gelatin-binding peptides to their surfaces. This parameter change in surface chemistry enables the cells to acquire specific binding affinity for damaged cartilage sites, transforming non-targeted cells into targeted therapeutic agents
2Measurement precision
If peptides with high binding affinity for gelatin are designed, then targeted delivery to damaged cartilage is improved, but peptide complexity increases
Solution Approach 1:
The patent segments the collagen-binding domain of MMP-2 into three functional modules (CB1, CB2, CB3), each with specific gelatin-binding capabilities. By combining these modular segments in different configurations, the patent creates peptides with tailored binding affinities without requiring entirely new peptide designs
Solution Approach 2:
The patent develops a universal set of gelatin-binding modules derived from MMP-2 that can be combined in various configurations to create multiple peptides with different binding characteristics. This modular approach allows one set of modules to serve multiple functions and generate multiple therapeutic agents
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 peptides demonstrate up to 14-fold higher binding affinity for type II collagen gelatin, facilitating accurate delivery and residency of MSCs and other agents to damaged cartilage and connective tissues, enhancing therapeutic outcomes.
Implementation Method 1
MMP-2 binds to gelatin through its Collagen Binding Domain (CBD)... The peptides demonstrate up to 14-fold higher binding affinity for type II collagen gelatin
Data Source
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AI summary
Provided are peptides, and conjugates comprising targeting peptides and payloads. The peptides comprise a plurality of modules corresponding to at least one of module 1, module 2, or module 3 of the collagen binding domain of a gelatinase, or a gelatin-binding fragment or variant thereof. The gelatinase may be MMP-2. The conjugates may be therapeutic or non-therapeutic. Medical uses of the peptides or therapeutic conjugates, and pharmaceutical compositions comprising these, are also provided, as are nucleic acids encoding the peptides.