Pluta Krzysztof, Kacprzak Magdalena Marta
Department of Hybrid Biosystems Engineering, Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warszawa, Poland.
Acta Biochim Pol. 2009;56(4):531-95. Epub 2009 Nov 23.
Despite the extensive research efforts over the past 25 years that have focused on HIV, there is still no cure for AIDS. However, tremendous progress in the understanding of the structure and biology of the HIV virus led to the development of safe and potent HIV-based transgene delivery vectors. These genetic vehicles are referred to as lentiviral vectors. They appear to be better suited for particular applications, such as transgene delivery into stem cells, compared to other viral- and non-viral vectors. This is because Lentivirus-based vectors can efficiently infect nondividing and slowly dividing cells. In the present review article, the current state of understanding of HIV-1 is discussed and the main characteristics that had an impact on vector design are outlined. A historical view on the vector concept is presented to facilitate discussion of recent results in vector engineering in a broader context. Subsequently, a state of the art overview concerning vector construction and vector production is given. This review also touches upon the subject of lentiviral vector safety and related topics that can be helpful in addressing this issue are discussed. Finally, examples of Lentivirus-based gene delivery systems and their applications are presented, with emphasis on animal transgenesis and human gene therapy.
尽管在过去25年里人们对艾滋病毒进行了广泛的研究,但艾滋病仍然无法治愈。然而,在对艾滋病毒的结构和生物学的理解方面取得了巨大进展,从而开发出了安全有效的基于艾滋病毒的转基因递送载体。这些基因载体被称为慢病毒载体。与其他病毒载体和非病毒载体相比,它们似乎更适合特定的应用,如将转基因递送至干细胞。这是因为基于慢病毒的载体能够有效地感染非分裂细胞和缓慢分裂的细胞。在本综述文章中,讨论了对HIV-1的当前理解状态,并概述了对载体设计有影响的主要特征。呈现了载体概念的历史观点,以便在更广泛的背景下便于讨论载体工程的最新结果。随后,给出了关于载体构建和载体生产的最新概述。本综述还涉及慢病毒载体安全性的主题,并讨论了有助于解决该问题的相关主题。最后,介绍了基于慢病毒的基因递送系统及其应用的实例,重点是动物转基因和人类基因治疗。