VectorLogics, Inc., 550 11th Street South, Birmingham, AL35294, USA.
Viruses. 2010 Aug;2(8):1681-1703. doi: 10.3390/v2081681. Epub 2010 Aug 16.
Adenovirus (Ad) vectors, in particular those of the serotype 5, are highly attractive for a wide range of gene therapy, vaccine and virotherapy applications (as discussed in further detail in this issue). Wild type Ad5 virus can replicate in numerous tissue types but to use Ad vectors for therapeutic purposes the viral genome requires modification. In particular, if the viral genome is modified in such a way that the viral life cycle is interfered with, a specific producer cell line is required to provide trans-complementation to overcome the modification and allow viral production. This can occur in two ways; use of a producer cell line that contains specific adenoviral sequences incorporated into the cell genome to trans-complement, or use of a producer cell line that naturally complements for the modified Ad vector genome. This review concentrates on producer cell lines that complement non-replicating adenoviral vectors, starting with the historical HEK293 cell line developed in 1977 for first generation Ad vectors. In addition the problem of replication-competent adenovirus (RCA) contamination in viral preparations from HEK293 cells is addressed leading to the development of alternate cell lines. Furthermore novel cell lines for more complex Ad vectors and alternate serotype Ad vectors are discussed.
腺病毒（Ad）载体，特别是血清型 5 的腺病毒载体，在基因治疗、疫苗和病毒疗法等广泛领域都极具吸引力（详见本期内容）。野生型 Ad5 病毒可以在多种组织类型中复制，但为了将 Ad 载体用于治疗目的，需要对病毒基因组进行修饰。具体而言，如果以干扰病毒生命周期的方式修饰病毒基因组，则需要特定的生产细胞系来提供转互补作用，以克服修饰并允许病毒产生。这可以通过两种方式实现：使用包含整合到细胞基因组中的特定腺病毒序列的生产细胞系进行转互补，或使用自然互补修饰的 Ad 载体基因组的生产细胞系。本综述重点介绍了用于补充非复制型腺病毒载体的生产细胞系，首先是 1977 年开发的用于第一代 Ad 载体的历史悠久的 HEK293 细胞系。此外，还解决了来自 HEK293 细胞的病毒制剂中复制型腺病毒（RCA）污染的问题，从而开发出了替代细胞系。此外，还讨论了用于更复杂的 Ad 载体和替代血清型 Ad 载体的新型细胞系。
