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

基本信息

批准号：
7670682
负责人：
ANDREW BAIRD
金额：
$ 9.72万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
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/7670682
关键词：
Ambulatory Care Antibodies Back Bacteriophages Becaplermin Binding Biological Markers Biological Products Biological Response Modifier Therapy Biology Bone Marrow Burn Trauma Caring Cell surface Cells Chimera organism Cicatrix Class Communities Complex Directed Molecular Evolution Discipline Drug Delivery Systems Drug Kinetics Epidermal Growth Factor Equipment and supply inventories Fibroblast Growth Factor Gene Delivery Gene Proteins Genes Growth Factor Growth Factor Gene Hematopoietic Human Lead Libraries Ligands Malignant Neoplasms Mesenchymal Stem Cells Methodology Methods Mining Modeling Molecular Biology Nucleic Acids Patients Peptide Library Peptides Phage Display Pharmaceutical Preparations Platelet-Derived Growth Factor Polymerase Chain Reaction Principal Investigator Proteins Proto-Oncogene Proteins c-sis Public Health Reagent Reconstructive Surgical Procedures Recovery Research Screening procedure Stem cells Stromal Cells Techniques Technology Testing Therapeutic Time United States Food and Drug Administration Workplace Wound Healing Wounds and Injuries analog base combinatorial design directed evolution experience improved in vivo in vivo Model injury and repair innovation multidisciplinary novel novel therapeutics pre-clinical precursor cell pressure progenitor response skills stem stem cell therapy therapeutic gene therapeutic target vector wound

项目摘要

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.

最初在某一研究领域（例如癌症）开发的技术有时引入速度很慢其他领域（例如伤口愈合）。该提案的总体目标是应用这样的一项进步，体内组合生物学，到伤口愈合（WH），从而创建和修改潜在的 WH 生物治疗药物。我们将通过 4 种技术筛选新疗法：（1）生物淘选，以鉴定靶向肽缺血性伤口，以便更好地输送药物； (2) SNAAP 筛选以创造药理学优化的生长具有改善伤口修复药代动力学的因子嵌合体； (3) LIVE恢复进化基因递送载体，针对 WH 环境进行基因优化，以及 (4) RBT 来识别细胞表面生物标记骨髓来源的前体细胞的特征可以迁移并植入伤口。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，它将为 WH 开辟新的场所研究。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签名并创造新的生物治疗剂。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中提供 (1) 创建、优化和分析库的具体经验（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) 引领伤口愈合社区转型的成功。对伤口愈合的影响：组合技术几乎可以应用于任何 WH 范式（例如外伤、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，并更好地了解了针对 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程序。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，尽量减少重建手术，改变疤痕形成并使患者返回工作场所。最初为其他学科开发的技术产生了增强、修改的全新方法并以一种可以影响各种不同类型伤口的方式了解 WH 反应。