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: 7137798
• 负责人: ANDREW BAIRD
• 金额: $ 94.4万
• 依托单位: LA JOLLA INST FOR MOLECULAR MEDICINE
• 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/7137798
• 关键词: animal tissue; bacterial virus; biomarker; biotechnology; biotherapeutic agent; cell surface receptors; combinatorial chemistry; confocal scanning microscopy; drug delivery systems; drug screening /evaluation; gene delivery system; growth factor; injury; laboratory mouse; laboratory rat; peptide library; phage display; pharmacokinetics; polymerase chain reaction; therapy design /development; wound healing

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(如癌症)开发的技术，有时在其他领域(如伤口愈合)推广缓慢。这项应用的总体目标是将体内组合生物学应用于创伤愈合，以创造和修改潜在的创伤修复生物疗法。我们将通过4项技术筛选新的治疗方法：(1)生物扫描，以确定缺血伤口的靶向多肽，以获得更好的药物输送；(2)SNAAP筛选，以创建药理上优化的生长因子嵌合体，并改进伤口修复的药代动力学；(3)活恢复，以进化出针对WH环境进行遗传优化的基因输送载体；(4)RBT，以鉴定骨髓来源的前体细胞上的细胞表面生物标记信号，这些细胞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。因为噬菌体展示可以回答研究问题，这是其他技术无法比拟的；它将为WH研究开辟新的场所。它将增加对WH机制的基本了解，识别内在有用的生物标记特征，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”，核心和项目的多学科技能提供(1)创建、优化和分析库(QA/QC，库存)的具体经验，(2)获得创伤愈合原型模型的途径，(3)设计、开发和测试理想原型屏幕的能力，以及(4)从点击到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、经过药理改进的基因载体，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。与公共卫生相关：门诊护理的进步增加了压力，要求加快正常的WH，最大限度地减少重建手术，改善疤痕形成，并将患者送回工作场所。最初为其他学科开发的技术产生了全新的方式来增强、修改和理解WH的反应，这种方式可以影响各种不同类型的创伤。