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: 7491591
• 负责人: ANDREW BAIRD
• 金额: $ 59.25万
• 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/7491591
• 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

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）开发的技术有时会缓慢地引入其他领域（例如伤口愈合）。 本申请的总体目标是将一种这样的进展（体内组合生物学）应用于伤口愈合（WH），以便产生和修饰潜在的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，以确定缺血性伤口的靶向肽，以更好地给药;（2）SNAAP筛选，以创建具有改善的伤口修复药代动力学的优化的生长因子嵌合体;（3）LIVE回收以进化基因递送载体，针对WH环境进行遗传优化，以及（4）RBT以鉴定骨髓来源的前体细胞上的细胞表面标记特征，所述前体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。 因为噬菌体展示技术可以回答其他技术无法回答的研究问题，它将为WH研究开辟新的领域。 它将增加对WH机制的基本理解，识别本质上有用的生物识别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”失败，核心和项目中的多学科技能提供（1）创建，优化和分析文库的特定经验（QA/QC，库存），（2）获得原型伤口愈合模型，（3）设计，开发和测试理想的原型屏幕和（4）命中导致伤口愈合社区的转型。 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，临床前候选人，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范例中具有辅助应用。 与公共卫生的相关性：门诊护理的进步增加了加速正常WH、尽量减少重建手术、改变瘢痕形成和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，这种方式可以影响各种不同类型的伤口。