Chandler L A, Gu D L, Ma C, Gonzalez A M, Doukas J, Nguyen T, Pierce G F, Phillips M L
Selective Genetics, Inc., 11035 Roselle Street, San Diego, CA 92121, USA.
Wound Repair Regen. 2000 Nov-Dec;8(6):473-9. doi: 10.1046/j.1524-475x.2000.00473.x.
Several growth factor proteins have been evaluated as therapeutic agents for the treatment of chronic dermal wounds. Unfortunately, most have failed to produce significant improvements in wound healing, in part due to ineffective delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ongoing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensure retention of the DNA vector as well as the therapeutic protein within the wound defect, we have evaluated matrix-enabled gene transfer for cutaneous wound repair (Gene Activated Matrix). Formulations consisting of bovine type I collagen mixed with adenoviral or plasmid gene vectors have been evaluated in 3 in vivo models. The therapeutic transgenes employed encode human platelet-derived growth factor-A or -B, proteins key to each phase of normal wound repair. Increased granulation tissue formation, vascularization, and reepithelialization have been shown compared to controls treated with collagen alone or collagen containing a reporter gene vector. Further enhancements of the tissue repair response have been achieved by combining matrix-enabled gene transfer with molecular targeting, in which the DNA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). These promising results support the clinical evaluation of gene activated matrices for the treatment of chronic dermal wounds.
几种生长因子蛋白已被评估作为治疗慢性皮肤伤口的治疗剂。不幸的是，大多数在伤口愈合方面未能产生显著改善，部分原因是递送无效以及在伤口缺损处滞留不佳。有人提出基因治疗可能通过持续的转录和翻译克服蛋白质治疗的局限性，从而延长治疗性蛋白质的可用性。考虑到确保DNA载体以及治疗性蛋白质在伤口缺损处滞留会带来更大益处，我们评估了用于皮肤伤口修复的基质介导基因转移（基因激活基质）。由牛I型胶原与腺病毒或质粒基因载体混合组成的制剂已在3种体内模型中进行了评估。所使用的治疗性转基因编码人血小板衍生生长因子-A或-B，这两种蛋白质是正常伤口修复各阶段的关键蛋白。与单独用胶原或含报告基因载体的胶原处理的对照相比，已显示出肉芽组织形成增加、血管生成增加和再上皮化增加。通过将基质介导基因转移与分子靶向相结合，已实现组织修复反应的进一步增强，其中DNA载体与生长因子配体（碱性成纤维细胞生长因子）偶联。这些有前景的结果支持对基因激活基质治疗慢性皮肤伤口进行临床评估。
