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

蛋白质、基因和细胞治疗的伤口愈合组合方法

• 批准号: 7573778
• 负责人: ANDREW BAIRD
• 金额: $ 48.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573778
• 关键词: Ambulatory Care; Biological Products; Biological Response Modifier Therapy; Biology; Bone Marrow; Burn Trauma; Cell surface; Cells; Chimera organism; Cicatrix; Communities; Discipline; Drug Delivery Systems; Drug Kinetics; Equipment and supply inventories; Gene Delivery; Gene Proteins; Genes; Growth Factor; Lead; Libraries; Malignant Neoplasms; Modeling; Molecular Biology; Patients; Peptides; Phage Display; Public Health; Reagent; Reconstructive Surgical Procedures; Recovery; Research; Screening procedure; Stromal Cells; Techniques; Technology; Testing; Therapeutic; Workplace; Wound Healing; combinatorial; design; experience; improved; in vivo; innovation; multidisciplinary; novel therapeutics; pre-clinical; precursor cell; pressure; progenitor; response; skills; stem; vector; wound

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.

描述（由申请人提供）：最初在一个研究领域（例如癌症）开发的技术有时在其他领域（例如伤口愈合）中的引入速度很慢。 该应用的总体目标是将体内组合生物学这一先进技术应用于伤口愈合（WH），以创建和修改潜在的 WH 生物治疗药物。 我们将通过4项技术筛选新疗法：（1）生物淘选，以确定缺血性伤口的靶向肽，以更好地进行药物输送； (2) SNAAP 筛选，以创建药理学优化的生长因子嵌合体，并改善伤口修复的药代动力学； (3) LIVE 恢复进化出一种基因传递载体，针对 WH 环境进行遗传优化；(4) RBT 识别骨髓源性前体细胞上的细胞表面生物标记特征，这些细胞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。 因为噬菌体展示可以像其他技术一样回答研究问题；它将开辟 WH 研究的新场所。 它将增加对 WH 机制的基本了解，识别本质上有用的生物标记特征并创造新的生物治疗药物。 需要多学科团队：噬菌体展示作为“分子生物学工具包”失败，而核心和项目中的多学科技能提供了（1）创建、优化和分析文库（QA/QC、库存）的具体经验，（2）获得原型伤口愈合模型，（3）设计、开发和测试理想原型屏幕的能力，以及（4）引领伤口愈合社区转型的能力。 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、药理学改进的基因载体，并更好地了解针对 WH 的祖细胞、干细胞和基质细胞。 它可以在各种不同的 WH 范式中具有辅助应用。 与公共卫生的相关性：门诊护理的进展增加了加速正常WH、尽量减少重建手术、改变疤痕形成以及使患者返回工作场所的压力。 最初为其他学科开发的技术产生了全新的方法来增强、修改和理解 WH 反应，从而可以影响各种不同类型的伤口。