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：
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
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/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

项目摘要

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开发的技术（例如癌症）有时会在其他领域引入慢速（例如伤口愈合）。该应用的总体目的是将一种这样的进步应用于体内组合生物学，以伤口愈合（WH），以创建和修改潜在的WH生物治疗剂。我们将使用4种技术筛选出新的治疗剂：（1）生物植物以识别靶向缺血性伤口的靶向肽，以更好地递送药物；（2）SNAAP筛查以创建具有改进的药代动力学的药理优化生长因子嵌合体以进行伤口修复；（3）实时恢复以进化基因递送载体，对WH MILIEU进行了遗传优化和（4）RBT，以鉴定骨髓衍生的前体细胞上的细胞表面生物标志性特征，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式。因为噬菌体显示可以回答研究问题，而不是其他技术；它将开设WH研究的新场地。它将增加对WH机制的基本理解，确定本质上有用的生物标记特征并创建新的生物治疗剂。 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. 对伤口愈合的影响：组合技术几乎可以应用于任何WH范式（例如创伤烧伤）。它将产生独特的研究试剂，临床前候选物，药理改进的基因载体，并更好地了解祖细胞，茎和基质细胞靶向WH。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，最小化重建手术，修改疤痕形成并将患者返回工作场所的压力。最初是为其他学科开发的技术，为增强，修改和理解WH响应的全新方法可能会影响各种不同的伤口。