携带感兴趣治疗基因的溶瘤单纯疱疹病毒的构建

Construction of Oncolytic Herpes Simplex Virus with Therapeutic Genes of Interest.

作者信息

Kahramanian Andranik, Kuroda Toshihiko, Wakimoto Hiroaki

机构信息

Department of Neurosurgery, Brain Tumor Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Methods Mol Biol. 2019;1937:177-188. doi: 10.1007/978-1-4939-9065-8_10.

DOI:10.1007/978-1-4939-9065-8_10

PMID:30706396

Abstract

Herpes simplex virus (HSV) is one of the most extensively studied oncolytic virus platforms. The recent FDA approval of talimogene laherparepvec (T-VEC) has been accelerating translational research of oncolytic HSV (oHSV) as a promising therapeutic for refractory cancers such as glioblastoma, the deadliest primary malignancy in the brain. The large genome size of HSV readily allows arming of oHSV by incorporating therapeutic transgenes within the virus, as exemplified by T-VEC carrying GM-CSF, thereby enhancing the anticancer activity of oHSV. Here we describe a bacterial artificial chromosome-based method for construction of an oHSV expressing a transgene, which we routinely use in the laboratory to create a number of different recombinant oHSV bearing either therapeutic or reporter genes.

摘要

单纯疱疹病毒（HSV）是研究最为广泛的溶瘤病毒平台之一。近期美国食品药品监督管理局（FDA）批准了talimogene laherparepvec（T-VEC），这加速了溶瘤性HSV（oHSV）作为难治性癌症（如胶质母细胞瘤，最致命的原发性脑恶性肿瘤）的一种有前景治疗方法的转化研究。HSV的大基因组大小使得通过在病毒内整合治疗性转基因来武装oHSV变得容易，以携带GM-CSF的T-VEC为例，从而增强了oHSV的抗癌活性。在此，我们描述了一种基于细菌人工染色体的构建表达转基因的oHSV的方法，我们在实验室中常规使用该方法来创建许多携带治疗性或报告基因的不同重组oHSV。