Hybrid Fusion Protein as a Dual Protease Inhibitor for the Healing of
Chronic Wounds
Abstract
Diseases bring about the need for interventions that pinpoint each
specific aspect of the illness. Commonly, remission of a complex disease
is accomplished by mixing treatments, medications, and therapeutics
together in a fashion where they may interact with each other negatively
as a systemic heterogeneous mixture. For example, chronic wounds are
very localized and have their own complex environment where tissue
deconstruction due to high levels of multiple proteases, such as HNE and
MMP-2, outweighs tissue reconstruction. This idea leads to the necessity
of a protein that contains low diffusivity rates for localized
treatment, strength against high concentrations of proteolytic species
that lead to degradation of short chain peptides, while encompassing
broad inhibitory effects against multiple proteases. Elastin-Like
Peptides (ELP’s) are an attractive, thermoresponsive, protein-based drug
delivery partner as they contain low diffusivity and serve as a stable
architecture for short chain peptide fusion. A novel elastin-like
peptide-based protein has been created to target the inhibition of both
HNE and MMP-2. As a biologic, this is unique as it is a protein with
specific biological activities against multiple proteases, ultimately
displaying the potential to mix and match differing biologically active
peptides within one amino acid sequence.