University of Waterloo, School of Pharmacy, Health Sciences Campus, Kitchener, ON, Canada.
Curr Gene Ther. 2009 Dec;9(6):434-58. doi: 10.2174/156652309790031148.
Numerous ovarian gene therapy strategies are in clinical phases based on concepts of replacement/ knock out of deregulated gene, suicide gene strategies, strengthening of the immune response against a tumor, inhibition of tumor angiogenesis and growth factors. Non-viral delivery systems have potential advantages over currently widely used viral vectors and other classical vectors for delivering therapeutic gene of interest. The present review provides a comprehensive overview of potential of various delivery systems currently in use. Non-viral formulations used in ovarian gene therapy include injecting naked DNA, liposomes, polyplexes, lipopolyplexes, nanoparticles, gene gun and ultrasound/microbubble mediated gene delivery. In addition to improving vector delivery, the DNA constructs need to be optimised for both efficient and long-term transgene expression. Minicircles using minimal immunological defined gene expression (MIDGE) technology, are a promising future alternative to plasmid for use in non-viral ovarian gene therapy in terms of biosafety, improved gene transfer, potential bioavailability, minimal size and little immune reaction. The review explores the best route of administration for ovarian cancer gene therapy given its peritoneal dissemination which poses a major challenge in treating ovarian cancer patients. Enhancement of therapeutic index can be further achieved by overcoming barriers both at cellular and nuclear levels. Selective tumor targeting with minimal toxicity using folate modified, incorporating nuclear localization signal and PEGylated stealth liposome's represents a popular approach and needs to be exploited in ovarian gene therapy.
许多卵巢基因治疗策略基于替代/敲除失调基因、自杀基因策略、增强对肿瘤的免疫反应、抑制肿瘤血管生成和生长因子的概念，处于临床阶段。非病毒传递系统在传递治疗性目的基因方面比目前广泛使用的病毒载体和其他经典载体具有潜在优势。本综述全面概述了目前使用的各种传递系统的潜力。用于卵巢基因治疗的非病毒制剂包括注射裸露 DNA、脂质体、多聚物、脂多聚物、纳米粒子、基因枪和超声/微泡介导的基因传递。除了改善载体传递外，还需要对 DNA 构建体进行优化，以实现高效和长期的转基因表达。使用最小免疫定义基因表达（MIDGE）技术的微环是一种很有前途的替代质粒的未来选择，可用于非病毒卵巢基因治疗，具有生物安全性、改善基因转移、潜在生物利用度、最小尺寸和很少的免疫反应。鉴于其腹腔扩散对治疗卵巢癌患者构成重大挑战，本综述探讨了卵巢癌基因治疗的最佳给药途径。通过克服细胞和核水平的障碍，可以进一步提高治疗指数。使用叶酸修饰、包含核定位信号和聚乙二醇化隐形脂质体的最小毒性进行选择性肿瘤靶向是一种很受欢迎的方法，需要在卵巢基因治疗中加以利用。
