SUSTAINED GENE TRANSFER FOR CHRONIC WOUND HEALING

持续基因转移促进慢性伤口愈合

• 批准号: 6071989
• 负责人: WEILIAM CHEN
• 金额: $ 14.92万
• 依托单位: CLEAR SOLUTIONS BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2002-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6071989
• 关键词: biodegradable product; biomaterial development /preparation; biotechnology; drug delivery systems; drug design /synthesis /production; gel; gene therapy; genetic manipulation; immunocytochemistry; plasmids; platelet derived growth factor; slow release drug; tissue /cell culture; topical drug application; wound healing

The incidence and prevalence of chronic topical wounds have significant implication on healthcare expenditure. Recent introduction of the first recombinant growth factor (Regranex[R], becaplermin, rhPDGF-BB) gel in the U.S. has improved the prospect for chronic wound treatment. Nevertheless, Regranex[R] has to be applied repeatedly during a prolonged course of treatment. New therapeutic modalities that could minimize the number of applications/interventions required for chronic wound are desirable. Topical gene transfer could circumvent the drawbacks associated with the current PDGF preparation. We have developed a biodegradable Hyaluronic Acid hydrogel film/matrix for delivering plasmid DNA. In this Phase I program, we will initially optimize the in vitro DNA release characteristics of the film and matrix. Thereafter, the longevity of these delivery vehicles for gene transfer will be studied using model fibroblast (CHO) and endothelial (HUVEC) cells. The program will be concluded by defining the longevity of the in vitro PDGF-B gene delivery from these vehicles in inducing cell proliferation. This single application film/matrix DNA sustained delivery system will provide substantially improved prospects for accelerating wound healing by overcoming the disadvantages associate with the current therapeutic modalities. PROPOSED COMMERCIAL APPLICATIONS: Chronic wounds causes major disability and have significant socioeconomic impact. Current treatment of chronic topical wounds requires multiple interventions and thus predisposes patients to discomforts, desiccation and infection which are detrimental to wound healing. This Phase I application is to demonstrate the feasibility of using a biodegradable hydrogel as a new sustained delivery therapeutic modality for gene transfer to accelerate the healing of chronic topical wounds, and thereby reduces the required treatment interventions to a minimal. Promising results obtained will expand this study into Phase II (animal studies) and thereafter clinical trial. This could result in a single application therapeutic modality for treating chronic topical wounds.

慢性局部伤口的发病率和患病率对医疗保健支出具有重要意义。在美国，最近引入了第一个重组生长因子（Regranex [R]，Becaplermin，RHPDGF-BB）凝胶，改善了慢性伤口治疗的前景。然而，在长时间的治疗过程中，必须反复应用Regranex [R]。希望最大程度地减少慢性伤口所需的应用/干预措施的新治疗方式。局部基因转移可以规避与当前PDGF制备相关的缺点。我们已经开发了一种可生物降解的透明质酸水凝胶膜/基质，用于输送质粒DNA。在此I阶段计划中，我们最初将优化膜和矩阵的体外DNA释放特性。此后，将使用模型成纤维细胞（CHO）和内皮细胞（HUVEC）细胞研究这些用于基因转移的输送车的寿命。该程序将通过定义从这些车辆诱导细胞增殖的体外PDGF-B基因递送的寿命来结束。这种单个应用膜/矩阵DNA持续递送系统将通过克服与当前治疗方式相关的缺点，从而为加速伤口愈合的前景提供大大改善的前景。拟议的商业应用：慢性伤害会导致重大残疾，并具有重大的社会经济影响。当前对慢性局部伤口的治疗需要多种干预措施，因此使患者患有不适，干燥和感染，这对伤口愈合有害。该阶段I的应用是为了证明使用可生物降解的水凝胶作为基因转移的一种新的持续递送治疗方式，以加速慢性局部伤口的愈合，从而将所需的治疗干预措施降低至最小。获得的有希望的结果将把这项研究扩展到II期（动物研究），然后将其扩展到临床试验中。这可能导致一种用于治疗慢性局部伤口的应用治疗方式。

项目成果

Preparation of hyaluronan-DNA matrices and films.

透明质酸-DNA 基质和薄膜的制备。

• DOI: 10.1101/pdb.prot071522
• 发表时间: 2012
• 期刊: Cold Spring Harbor protocols
• 作者: Chen,Weiliam

Characterization of DNA-hyaluronan matrix for sustained gene transfer.

用于持续基因转移的 DNA-透明质酸基质的表征。

• DOI: 10.1016/s0168-3659(03)00175-5
• 发表时间: 2003
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Kim,Angela;Checkla,DanielM;Dehazya,Philip;Chen,Weiliam
• 通讯作者: Chen,Weiliam