Targeted Gene Therapy Using Synthetic Vectors

描述（由申请人提供）：基因治疗是治疗源于遗传性疾病的人类疾病（例如，癌症）。然而，基因治疗作为一种可行的治疗方式的应用中的一个主要障碍是安全和有效的基因转移载体的发展。病毒和非病毒（合成）载体都在积极研究中。迄今为止，对病毒载体的研究远多于对合成载体的研究。然而，随着研究的进展，合成载体呈现出优于病毒载体的几个优点。这项工作的目标是开发一种新的非病毒的，有针对性的，基因转移载体的肿瘤性疾病的基因治疗。对于I期原理验证，我们选择叶酸作为表达叶酸受体的卵巢癌细胞模型的靶向部分用于体外实验。我们的新的基因转移载体将进行评估的潜在治疗卵巢癌进行了一系列的体外评估，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，复合物的稳定性，并在体外基因转移。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，卵巢癌的发生频率为每年约23，000例新发病例，生存率低于50%。卵巢癌的现有治疗方式由于早期检测的困难和疾病的进展性而具有有限的成功率。基因治疗，无论是单独使用或与其他治疗方式相结合，提供了新的承诺，有效地控制癌症是难治性的常规治疗方案。一种新的癌症靶向基因转移剂的基础上提出的纳米粒子脂质样支架将是一个受欢迎的除了不断增长的军火库的癌症治疗。

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.