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: 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
• 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

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.

最初在一个研究领域开发的技术（例如癌症）有时会引入缓慢 在其他领域（例如伤口愈合）。该提案的总体目的是在 体内组合生物学，伤口愈合（WH），以创建和修改潜在的生物治疗剂。 我们将使用4种技术筛选新的治疗剂：（1）生物动物以识别针对肽的肽 缺血性伤口可更好地输送药物； （2）SNAAP筛选以创建药理优化的增长 因子嵌合体，改善了用于伤口修复的药代动力学； （3）实时恢复以进化基因 递送载体，针对WH Milieu进行了遗传优化和（4）RBT以识别细胞表面生物标记 可以迁移到伤口的骨髓衍生前体细胞上的特征。 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，例如没有其他技术，它将开放新的场所 研究。它将增加对WH机制的基本了解，确定本质上有用的生物标记 签名并创建新的生物治疗剂。 多学科团队的需求：噬菌体显示失败是“分子生物学套件”和多学科技能 在核心和项目中，（1）特定的经验来创建，优化和分析库（QA/QC，，， 库存），（2）访问原型伤口愈合模型，（3）设计，开发和测试理想的能力 原型屏幕和（4）引导伤口愈合社区转变的命中。 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）。它将在药理学上生成独特的研究试剂，临床前候选者 改善了基因载体以及对祖细胞，茎和基质细胞靶向WH的更好理解。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， 最大程度地减少重建手术，修饰疤痕形成并将患者返回工作场所。 最初是为其他学科开发的技术，为增强，修改生成了全新的方法 并以一种可能影响各种伤口的方式了解WH反应。