Development and use of gene transfer for treatment of cardiovascular disease
Development and use of gene transfer for treatment of cardiovascular disease
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DOI：
10.1046/j.1540-8191.2002.01011.x
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发表时间：
2002-11-01
影响因子：
1.6
通讯作者：
Baker, AH
中科院分区：
文献类型：
--
作者：
Baker, AH
基因治疗有望用于治疗心血管疾病，对于这些疾病，有效的药物治疗不足或不可用。最近的研究表明，修改目前的基因传递系统结合使用有效的治疗基因可能最终成功的临床血管基因治疗。尽管静脉移植失败等某些应用可能最适合治疗基因的短期短暂过表达，但包括人类原发性高血压和动脉粥样硬化在内的其他疾病需要基因的持续过表达。因此，用于将基因递送至体内所需位点的载体系统的设计和使用需要仔细考虑。病毒和非病毒基因治疗载体都显示出将基因转移到血管细胞中的低效率，并且表现出缺乏选择性，因为载体对其他细胞和组织具有天然向性。最近的工作集中在血管细胞选择性基因治疗载体的设计，开发和实用性，用于不同的和不同的血管基因治疗方案。利用噬菌体展示技术，我们已经分离出小肽配体，介导选择性结合血管内皮细胞或血管平滑肌细胞。当被工程化到腺病毒（Ad）或腺相关病毒（AAV）载体中时，候选肽使病毒能够选择性地结合所需的细胞类型，从而产生新的血管细胞选择性基因转移。由于临床前研究突出了血管基因治疗的潜力以及确定潜在的陷阱，疾病选择性基因治疗的发展将提高基因治疗的安全性和效率，以供未来的临床使用。
Gene therapy holds promise for the treatment of cardiovascular diseases for which effective pharmacological therapies are insufficient or unavailable. Recent studies have suggested that modification of current gene delivery systems combined with the use of efficacious therapeutic genes may ultimately be successful for clinical vascular gene therapy. Although certain applications such as vein-graft failure may be best suited for short-term transient overexpression of therapeutic genes, other disorders including human essential hypertension and atherosclerosis require sustained overexpression of genes. Hence, design and use of vector systems for delivery of genes to the required site in vivo requires careful consideration. Both viral and nonviral gene therapy vectors show low efficiency for gene transfer into vascular cells and demonstrate a lack of selectivity, as vectors have natural tropism for other cells and tissues. Recent work has focused on the design, development, and utility of vascular cell-selective gene therapy vectors for use in distinct and diverse vascular gene therapy scenarios. Using phage display technology we have isolated small peptide ligands that mediate selective binding to either vascular endothelial cells or vascular smooth muscle cells. When engineered into either adenoviral (Ad) or adeno-associated viral (AAV) vectors, candidate peptides enabled the virus to selectively bind to the desired cell type thus generating novel vascular cell-selective gene transfer. As preclinical studies have highlighted both the potential for vascular gene therapy as well as defining the potential pitfalls, the development of disease-selective gene therapeutics will increase safety and efficiency of gene therapy for future clinical use.