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

最初在一个研究领域（如癌症）开发的技术，有时引进缓慢 在其他领域（如伤口愈合）。本提案的总体目标是应用一种这样的先进技术， 体内组合生物学应用于伤口愈合（WH），从而产生和修饰潜在的WH生物治疗剂。 我们将用4种技术筛选新的治疗方法：（1）生物淘选，以确定靶向肽， 缺血性伤口更好的药物输送;（2）SNAAP筛选，以创造最佳的生长 因子嵌合体具有改善的伤口修复药代动力学;（3）LIVE恢复以进化基因 递送载体，针对WH环境进行遗传优化，以及（4）RBT以鉴定细胞表面生物标记 在骨髓来源的前体细胞上的签名，其可以迁移到伤口并植入伤口。 创新：组合技术从未应用于伤口愈合范例。因为 噬菌体展示技术可以回答其他技术无法回答的研究问题，它将为WH开辟新的途径， research.它将增加对WH机制的基本理解，识别本质上有用的标记 签名并创建新的生物识别剂。 需要多学科团队：噬菌体展示作为“分子生物学试剂盒”和多学科技能失败 在核心和项目提供（1）具体的经验，以创建，优化和分析库（QA/QC， 库存），（2）获得原型伤口愈合模型，（3）设计，开发和测试理想的能力 原型屏幕和（4）命中导致伤口愈合社区的转变。 对伤口愈合的影响：组合技术可应用于几乎任何WH范例（例如， 创伤、烧伤）。它将产生独特的研究试剂，临床前候选药物， 改进的基因载体和更好地了解祖细胞，干细胞和基质细胞靶向WH。它 可以在各种不同的WH范例中有辅助应用。 与公共卫生的相关性：门诊护理的进展增加了加速正常WH的压力， 最大限度地减少重建手术，减少疤痕形成，让患者重返工作场所。 最初为其他学科开发的技术，产生了全新的方法来增强，修改 并了解WH反应的方式，可以影响各种不同类型的伤口。

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 proposal 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 impacts all kinds of different kinds of wounds.