Viral vectors and nucleic acids for regulated gene therapy

The present invention relates generally to the field of somatic gene therapy. The present invention provides nucleic acid constructs comprising a transgene encoding a therapeutic protein, a tetracycline response aptamer enzyme sequence, and an inverted terminal repeat (ITR). The nucleic acid constructs can be transferred to a subject in need thereof in the form of a viral vector, particularly in the form of an adeno-associated virus (AAV) vector. The Tet response aptamer enzyme sequence allows for strict controlled expression of transgenes in a subject, thereby avoiding toxic and side effects. The nucleic acid constructs and viral vectors comprising the same are particularly useful in the treatment of proliferative diseases such as cancer. 本发明一般涉及体细胞基因治疗的领域。本发明提供了这样的核酸构建体，其包含编码治疗性蛋白的转基因、四环素应答适体酶序列和反向末端重复序列(ITR)。核酸构建体可以病毒载体的形式，特别是腺相关病毒(AAV)载体的形式转移至有需要的受试者。Tet应答适体酶序列允许转基因在受试者中的严格控制表达，由此避免毒副作用。核酸构建体和包含其的病毒载体特别可用于增生性疾病如癌症的治疗。