NEW DNA REPAIR LIPOSOMES FOR PREVENTION OF SKIN CANCER

皮肤癌在美国已经成为一种流行病，其中大部分来自于 紫外线对DNA的伤害应用遗传学已经开发了一种新的方法， 使用脂质体递送的DNA修复酶来防止UV诱导的 皮肤癌第一代产品T4N5脂质体， III期临床试验。该提案旨在制定下一个 产生DNA修复酶，使用一种新的光裂合酶， 特异性的<6-4>光产物，和一种新的内切核酸酶， 对环丁烷嘧啶二聚体和<6-4> 照片产品第一阶段的计划是证明以下方面的可行性： 将这些新酶封装在脂质体中。这包括 开发新的试剂和测定其活性的方法， 测定这些酶在脂质体中的活性和稳定性。如果 这两种酶中的任何一种都被证明是有用的，那么计划就是 进入第二阶段测试，以确定其在细胞中的有效性 文化和动物系统。 拟定商业应用： 该研究将直接导致临床前和临床测试 预防皮肤癌的新产品。这些收集的数据 研究将用于评价新的DNA修复脂质体的活性， 稳定性和安全性，并将用于文件中，以支持 研究性新药申请。批准的光老化和皮肤 癌症预防产品每年的销售额可达2亿美元。

Skin cancer has become an epidemic in the US, and most of it arises from solar UV damage to DNA. Applied Genetics has developed a new approach, using DNA repair enzymes delivered by liposomes to prevent UV-induced skin cancer. The first generation of product, T4N5 liposomes, is in Phase III clinical testing. This proposal is to develop the next generation of DNA repair enzymes, using a new photolyase with specificity for the <6-4> photoproduct, and a new endonuclease with specificity for both cyclobutane pyrimidine dimers and <6-4> photoproducts. The Phase I plan is to demonstrate the feasibility of encapsulating these new enzymes in liposomes. This includes the development of new reagents and assays for their activities, and to assay the activity and stability of these enzymes in liposomes. If either of both of these enzymes prove useful, then the plan is to advance to the Phase II testing to establish their effectiveness in cell culture and animal systems. PROPOSED COMMERCIAL APPLICATION: The research will lead directly to the pre-clinical and clinical testing of new products to prevent skin cancer. The data gathered in these studies will be used to evaluate new DNA repair liposomes for activity, stability and safety, and will be used in documents to support an Investigational New Drug application. Approved photoaging and skin cancer prevention products can have sales of $200 million annually.