A Combinatorial Approach to Wound Healing for Protein, Gene and Cell Therapeutics

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DESCRIPTION (provided by applicant): Technologies originally developed in one field of research (e.g. cancer), is sometimes slow to be introduced in other fields (e.g. wound healing). The overall objective of this application is to apply one such advance, in vivo combinatorial biology, to wound healing (WH) so as to create and modify potential WH biotherapeutics. We will screen for new therapeutics with 4 technologies: (1) Biopanning to identify targeting peptides for the ischemic wound for better drug delivery; (2) SNAAP screening to create pharmacologically optimized growth factor chimera with improved pharmacokinetics for wound repair; (3) LIVE recoveries to evolve a gene delivery vector, genetically optimized for the WH milieu and (4) RBT to identify cell surface biomarking signatures on bone marrow-derived precursor cells that can migrate to and engraft the wound. Innovation: Combinatorial technologies have never been applied to a wound healing paradigm. Because phage display can answer research questions like no other technique; it will open new venues of WH research. It will increase basic understanding of WH mechanisms, identify intrinsically useful biomarking signatures and create new biotherapeutic agents. Need for a multidisciplinary team: Phage display fails as a "molecular biology kit" and multidisciplinary skills in cores and projects provide (1) specific experience to create, optimize and analyze libraries (QA/QC, inventory), (2) access to prototypic wound healing models, (3) the ability to design, develop and test ideal prototypic screens and (4) the hit to lead transformation for the wound healing community. Impact on wound healing: Combinatorial techniques could be applied to virtually any WH paradigm (e.g. trauma burns). It will generate unique research reagents, preclinical candidates, pharmacologically improved gene vectors and a better understanding of progenitor, stem and stromal cell targeting to WH. It can have ancillary applications in all kinds of different WH paradigms. Relevance to public health: Progress in ambulatory care increases pressures to accelerate normal WH, minimize reconstructive surgery, modify scar formation and return the patient to the workplace. Technologies originally developed for other disciplines, generates completely new ways to enhance, modify and understand the WH response in a fashion that can impact all kinds of different kinds of wounds.