The use of DNA viruses as vectors for gene therapy.
The use of DNA viruses as vectors for gene therapy.
复制标题
使用DNA病毒作为基因治疗的载体。
作者：
M. Ali;N. Lemoine;C. Ring
有效转移潜在的治疗基因到确定的细胞群体的需要刺激了基于病毒的载体的发展。迄今为止，大部分的努力都花在了含RNA的逆转录病毒上。然而，这些病毒具有许多缺点，包括不能感染非分裂细胞以及由于随机染色体整合而具有致癌性和宿主细胞基因插入诱变的潜力。这些缺点导致了基于含DNA病毒如腺病毒、单纯疱疹病毒和细小病毒的载体的开发。这些病毒具有许多有利于它们在基因治疗中使用的属性。例如，腺病毒由于其对呼吸道上皮的天然亲和力而首先被认为是用于肺部病症的遗传治疗的潜在载体。然而，其他特征，包括它们以高滴度制备的能力、指导高水平外源基因表达的能力以及它们的染色体外存在，导致它们被开发用于治疗许多其他疾病。在许多研究中，腺病毒载体已被证明有效地感染靶细胞群体，并在没有显著毒性的情况下以治疗水平表达蛋白质。单纯疱疹病毒能够以潜伏状态驻留在神经元中，而且似乎不会影响正常的细胞生理机能，这引发了人们对这种病毒作为治疗神经系统疾病的潜在载体的兴趣。细小病毒的一个亚组，即腺相关病毒，具有在确定的染色体位置整合的倾向，并且可能代表逆转录病毒的更安全的替代物。
The need for efficient transfer of potentially therapeutic genes to defined cell populations has stimulated the development of vectors based on viruses. To date, most effort has been spent on the RNA-containing retroviruses. These viruses, however, possess a number of disadvantages including an inability to infect nondividing cells as well as having potential for oncogenicity and insertional mutagenesis of host cell genes due to random chromosomal integration. These disadvantages have led to the development of vectors based on DNA-containing viruses such as adenovirus, herpes simplex virus and parvovirus. These viruses possess a number of attributes favourable to their use in gene therapy. Adenoviruses, for example, were first considered as potential vectors for the genetic treatment of lung conditions due to their natural affinity for respiratory epithelium. However, other features including their ability to be prepared at high titres, to direct high levels of foreign gene expression and their extrachromosomal existence has resulted in their development for the treatment of numerous other diseases. In many studies, adenovirus vectors have been shown to efficiently infect target cell populations and to express proteins at therapeutic levels in the absence of significant toxicity. The ability of herpes simplex virus to reside in neurons in a latent state that does not appear to affect normal cellular physiology has sparked interest in this virus as a potential vector in the treatment of neurological disorders. A subgroup of parvoviruses, namely the adeno-associated viruses, have a prediliction for integration at a defined chromosomal location and may represent a safer alternative to retroviruses.