应用组织特异微RNA构建更加安全的腺病毒

Building Safer Adenovirus by Using of Tissue-specific MicroRNA

溶瘤腺病毒是目前最有潜力的肿瘤治疗病毒载体之一,但其在应用过程中会产生比较严重的毒副作用,特别是肝脏毒性。为了更好地针对组织靶标,需要制备更加安全、有效的溶瘤腺病毒。近年来,科学家使用微RNA(miRNA)调控基因表达系统,将若干拷贝数的组织特异性miRNAs对应的靶序列加入到腺病毒复制早期必需基因E1基因表达盒的3'非翻译区,在转录后水平调控病毒复制。这种方法能有效消除腺病毒的毒副作用,进一步提高腺病毒使用的安全性。

Oncolytic adenovirus has been considered as one of the most potential agents for cancer treatment, though in the process of application, it is still associated with serious toxic and side effects, especially hepatotoxicity. For the purpose of better aiming at the target, oncolytic adenovirus with better safety and effect is needed to be prepared. In recent years, many scientists utilized microRNA-regulated gene expression system to build safer and effective adenoviruses. Several copies of complementary sequences for tissue or cellspecific microRNAs are incorporated into the 3 ＇-untranslated region of the E1 gene expression cassette to con- trol post-transcriptional adenovims replication. This strategy can effectively eliminate the toxic and side effects and significantly improve the safety profiles.