Roy S, Shirley P S, McClelland A, Kaleko M
Genetic Therapy Inc., Gaithersburg, Maryland 20878, USA.
J Virol. 1998 Aug;72(8):6875-9. doi: 10.1128/JVI.72.8.6875-6879.1998.
Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5.
对腺病毒的免疫是成功进行基因治疗需要克服的一个重要障碍。针对衣壳蛋白的抗体的存在会阻碍腺病毒载体在体内的有效给药。我们测试了是否可以用一种编码来自不同腺病毒血清型（Ad12）六邻体序列的载体来克服对特定血清型腺病毒（Ad5）的免疫。我们成功构建了一种具有嵌合Ad5-Ad12六邻体的腺病毒载体，该载体不会被用Ad5免疫的C57BL/6小鼠的血浆中和。该载体还能够转导先前用Ad5免疫的C57BL/6小鼠的肝脏。
