Targeted Gene Therapy Using Synthetic Vectors

描述（由申请人提供）：基因治疗是一种很有前途的方法，用于治疗源于遗传疾病的人类疾病（如癌症）。然而，将基因治疗作为一种可行的治疗方式的主要障碍是开发安全有效的基因转移载体。目前正在积极研究病毒和非病毒（合成）载体。迄今为止，对病毒载体的研究远远多于对合成载体的研究。然而，随着研究的不断深入，合成载体与病毒载体相比具有许多优势。本研究的目标是开发一种新的非病毒、靶向性的基因转移载体，用于肿瘤疾病的基因治疗。对于I期原理验证，我们选择叶酸作为叶酸受体表达卵巢癌细胞模型的靶向片段进行体外实验。我们的新基因转移载体将通过一系列的体外评估来评估其治疗卵巢癌的潜力，以表征载体并确定两个报告基因的相对基因转移效率。我们将筛选载体的DNA凝聚，复杂的稳定性，和体外基因转移。卵巢癌是美国第二常见和最致命的妇科恶性肿瘤。根据美国癌症协会的数据，卵巢癌每年约有23000例新病例，生存率不到50%。由于卵巢癌的早期发现困难和疾病的进行性，现有的治疗方式成功率有限。基因治疗，无论是单独使用还是与其他治疗方式联合使用，都为有效控制常规治疗方案难以治愈的癌症提供了新的希望。本文提出的一种基于纳米颗粒脂质样支架的新型癌症靶向基因转移剂将是日益增长的癌症治疗武器库的一个受欢迎的补充。

DESCRIPTION (provided by applicant): Gene therapy is a promising approach for treatment of human diseases rooted in genetic disorders (e.g., cancer). However, a major obstacle in the application of gene therapy as a viable treatment modality is the development of safe and effective gene transfer vectors. Both viral and non-viral (synthetic) vectors are actively being studied. To date, viral vectors have been studied much more than synthetic vectors. However, as research progresses, synthetic vectors are presenting themselves with several advantages over viral vectors. The goal of this proposed effort is to develop a new non-viral, targeted, gene transfer vector for gene therapy of neoplastic diseases. For the Phase I proof-of-principle, we have chosen folic acid as a targeting moiety for folate receptor expressing ovarian cancer cell model for in vitro experiments. Our novel gene transfer vectors will be evaluated for the potential treatment of ovarian cancer by conducting a series of in vitro assessments to characterize the vectors and determine the relative gene transfer efficiency of two reporter genes. We will screen vectors for DNA condensation, complex stability, and in vitro gene transfer. Ovarian cancer is the second most common and the deadliest gynecologic malignancy in the US. According to the American Cancer Society, ovarian cancer occurs at a frequency of ~23,000 new cases per year with a less than 50% survival rate. Existing treatment modalities for ovarian cancer have limited success rates due to difficulties in early detection and the progressive nature of the disease. Gene therapy, either used alone or in combination with other therapeutic modalities, provides new promises for effective control of cancers that are refractory to conventional therapeutic regimens. A new cancer-targeting gene tranfer agent based on a nanoparticle lipid-like scaffold as proposed here would be a welcome addition to the growing arsenal of cancer therapies.