Berkowitz R D, Ilves H, Plavec I, Veres G
SyStemix Incorporated, 3155 Porter Drive, Palo Alto, California, 94304, USA.
Virology. 2001 Jan 5;279(1):116-29. doi: 10.1006/viro.2000.0659.
Efficient transfer of therapeutic genes into nondividing human cells can be accomplished by inserting the genes into lentiviruses and infecting the cells with the modified viruses. The most developed lentivirus gene transfer systems are based on HIV-1, but because of the widespread HIV epidemic, the use of HIV-based vectors for gene therapy may be associated with a safety risk. In an attempt to find another lentivirus which can transduce human cells and might be safer than HIV-1, we generated gene transfer constructs based on the sheep lentivirus Visna. Molecular analysis of the constructs in a transient production system indicated that Visna produced as many mature virus particles as did HIV-1. Moreover, the virus particles incorporated a heterologous surface protein marker-gene-containing vector RNAs as efficiently as did HIV-1. However, the Visna virus transduced target cells poorly because of defects in reverse transcription and integration of the vector. Further modifications must be made to the Visna gene transfer system if the system is to be used in clinical gene therapy applications.
通过将治疗性基因插入慢病毒并使用修饰后的病毒感染细胞，可实现将治疗性基因高效转移至不分裂的人类细胞中。目前最成熟的慢病毒基因转移系统基于HIV-1，但鉴于HIV的广泛流行，使用基于HIV的载体进行基因治疗可能存在安全风险。为了寻找另一种能够转导人类细胞且可能比HIV-1更安全的慢病毒，我们构建了基于绵羊慢病毒维斯纳病毒（Visna）的基因转移载体。在瞬时生产系统中对这些载体进行分子分析表明，维斯纳病毒产生的成熟病毒颗粒数量与HIV-1相同。此外，病毒颗粒整合含异源表面蛋白标记基因的载体RNA的效率与HIV-1相当。然而，由于载体逆转录和整合存在缺陷，维斯纳病毒对靶细胞的转导效果较差。如果要将维斯纳基因转移系统用于临床基因治疗应用，必须对其进行进一步改进。
