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

最初在一个研究领域(例如癌症)开发的技术，有时引进得很慢 在其他领域(如伤口愈合)。这项提案总体目标是将其中一项进步应用于 体内组合生物学，以伤口愈合(WH)，从而创造和修改潜在的WH生物疗法。 我们将用4种技术筛选新的治疗方法：(1)生物扫描，以确定靶向多肽 用于更好的药物输送的缺血伤口；(2)SNAAP筛选以创造药物优化的生长 具有改进的伤口修复药代动力学的因子嵌合体；(3)进化基因的活恢复 递送载体，针对WH环境和(4)RBT进行遗传优化以识别细胞表面生物标记 骨髓来源的前体细胞上的签名，可以迁移到伤口并植入伤口。 创新：组合技术从未被应用于伤口愈合范例。因为 噬菌体展示能够回答研究问题，这是其他任何技术都无法比拟的，它将开启世界卫生组织的新天地 研究。它将增加对WH机制的基本理解，识别本质上有用的生物标记 签名并创造新的生物治疗剂。 需要一个多学科团队：噬菌体展示不能作为“分子生物学工具包”和多学科技能 在核心和项目中提供(1)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 原型筛选和(4)引领伤口愈合社区转型的热门。 对伤口愈合的影响：组合技术几乎可以应用于任何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，药理学 改进了基因载体，更好地了解了针对WH的祖细胞、干细胞和基质细胞靶向。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：门诊护理的进步增加了加快正常卫生保健的压力， 最大限度地减少重建手术，减少疤痕形成，让患者回到工作场所。 最初为其他学科开发的技术，产生了全新的增强、修改 并以一种可以影响各种不同伤口的方式理解WH的反应。

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.