GROWTH FACTOR GENE THERAPY FOR WOUND HEALING

用于伤口愈合的生长因子基因疗法

• 批准号: 2867523
• 负责人: John Doukas
• 金额: $ 10万
• 依托单位: SELECTIVE GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2867523
• 关键词: Adenoviridae; collagen; enzyme linked immunosorbent assay; gene expression; gene therapy; genetic transduction; hepatocyte growth factor; histology; immunocytochemistry; platelet derived growth factor; polymerase chain reaction; technology /technique development; transfection /expression vector; vascular endothelial growth factors; wound healing

The use of growth factors for wound treatment has produced only minimal clinical benefit. One difficulty is achieving adequate therapeutic levels at wound sites for prolonged times. Gene therapy offers a solution to this problem by allowing for sustained growth factor production. Previously, we developed a method to redirect adenoviral vector tropism to fibroblast growth factor (FGF) receptors, allowing for their delivery to activated and proliferating cells such as those present in wounds. We now propose to apply this approach to wound healing, and to augment the retention of growth factors by delivering vectors within collagen gels. Specific Aim #1 will expand upon preliminary in vitro data to characterize cellular production and release of platelet derived growth factor (PDGF), our primary therapeutic candidate. Specific Aim #2 will expand upon in vivo data to characterize PDGF production and de novo tissue formation in order to confirm the efficacy of our approach. Finally, Specific Aim #3 will examine alternative growth factors that have not been adequately assessed for wound healing efficacy using in vivo models. The data generated will establish the groundwork required for the future application of this therapeutic approach in Phase II studies and clinical trials. PROPOSED COMMERCIAL APPLICATIONS: These experiments will permit us to develop novel therapeutics for the treatment of acute and chronic wounds. Such wounds which cause significant morbidity and can lead to mortality. Presently, few therapeutic options allow for the augmentation of soft tissue repair, especially in patients with chronic ulcers. The use of targeted gene therapy and semi- solid matrices offer the possibility of delivering novel and potent therapeutic agents, with improved specificity and retention offer existing treatments.

生长因子用于伤口治疗仅产生了最小的临床益处。 一个困难是长时间在伤口部位达到足够的治疗水平。 Gene Therapy通过允许持续生长因子产生来解决此问题。以前，我们开发了一种方法，将腺病毒载体的逆向媒介物向成纤维细胞生长因子（FGF）受体重新定向，从而使其递送到激活和增殖的细胞（例如伤口中存在的细胞）。现在，我们建议将这种方法应用于伤口愈合，并通过在胶原凝胶中传递向量来增加生长因子的保留。特定目标＃1将扩展到初步的体外数据，以表征我们主要治疗候选者的细胞产生和血小板衍生生长因子（PDGF）的释放。特定的目标＃2将扩展体内数据，以表征PDGF产生和从头组织形成，以确认我们方法的功效。最后，特定的目标＃3将检查尚未通过体内模型对伤口愈合功效进行充分评估的替代生长因子。生成的数据将确定这种治疗方法在II期研究和临床试验中的未来应用所需的基础。拟议的商业应用：这些实验将使我们能够开发出新的治疗急性和慢性伤口的治疗疗法。这种引起明显发病并可能导致死亡率的伤口。目前，很少有治疗选择可以增加软组织修复，尤其是在慢性溃疡患者中。靶向基因疗法和半固定基质的使用提供了提供新颖和有效的治疗剂的可能性，具有提高的特异性和保留剂提供了现有的治疗方法。