Dematteo R P, McClane S J, Fisher K, Yeh H, Chu G, Burke C, Raper S E
Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
J Surg Res. 1997 Oct;72(2):155-61. doi: 10.1006/jsre.1997.5096.
Recombinant adenovirus accomplishes highly efficient gene transfer in vivo. Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express the lacZ marker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.
重组腺病毒可在体内实现高效的基因转移。如果转基因表达是可诱导的且局限于靶组织，腺病毒载体将成为更具吸引力的基因治疗载体。在这些研究中，我们假设通过使用组织特异性转录启动子可以实现重组腺病毒的选择性转基因表达。构建了一种复制缺陷型腺病毒载体，使其在小鼠胰腺淀粉酶启动子的控制下表达lacZ标记基因。该载体的表达仅发生在新生和成年小鼠的胰腺中，而具有组成型启动子的类似载体在多个器官中实现了转基因表达。在腺病毒构建体中，淀粉酶启动子保留了被地塞米松和胰岛素诱导的能力。该模型将作为选择性和可诱导腺病毒转基因表达的范例。
