Rendahl K G, Leff S E, Otten G R, Spratt S K, Bohl D, Van Roey M, Donahue B A, Cohen L K, Mandel R J, Danos O, Snyder R O
Cell Genesys Inc., Foster City, CA 94404, USA.
Nat Biotechnol. 1998 Aug;16(8):757-61. doi: 10.1038/nbt0898-757.
Control of gene expression is important to gene therapy for purposes of both dosing and safety. In vivo regulation of gene expression was demonstrated following co-injection of two separate recombinant adeno-associated virus vectors, one encoding an inducible murine erythropoietin transgene and the other a transcriptional activator, directly into the skeletal muscle of adult immunocompetent mice. Transcription was controlled by systemic administration or withdrawal of tetracycline over an 18 week period, demonstrating that the two vectors were capable of transducing the same cell. Cellular or humoral immune responses against the transactivator protein were not detected.
基因表达的调控对于基因治疗的剂量和安全性而言都很重要。在成年免疫活性小鼠的骨骼肌中直接共注射两种单独的重组腺相关病毒载体后，证明了基因表达的体内调控。其中一种载体编码可诱导的小鼠促红细胞生成素转基因，另一种载体编码转录激活因子。通过在18周内全身给药或停用四环素来控制转录，这表明这两种载体能够转导同一细胞。未检测到针对反式激活蛋白的细胞免疫或体液免疫反应。
