Gene Therapy Program. University of Navarra-CIMA, Navarra Institute of Health Research, 31008 Pamplona, Navarra, Spain.
Int J Mol Sci. 2020 May 21;21(10):3643. doi: 10.3390/ijms21103643.
The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or "gutless". Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.
腺病毒作为基因传递工具的适应性导致了高容量腺病毒载体（HC-AdVs）的发展，也称为辅助依赖性或“无肠”。与早期（E1/E3 缺失载体）相比，HC-AdVs 保留了相关特征，如遗传稳定性、体内转导的显著功效和高滴度生产。更重要的是，HC-AdVs 基因组中缺乏病毒编码序列将克隆容量扩展到 37 Kb，并允许转基因在非分裂细胞中长期存在于染色体外。这些特性在基因补充和基因校正领域开辟了广泛的治疗机会，在过去的二十年中已经在临床前水平进行了探索。在此期间，生产方法得到了优化，以获得临床实施所需的产量、纯度和可靠性。更好地理解炎症反应和实施控制它们的方法增加了这些载体的安全性。我们将回顾将有趣的研究工具转化为可靠载体平台的最重大成就，这可能有助于克服基因治疗领域的当前限制。
