Lo K M, Biasolo M A, Dehni G, Palú G, Haseltine W A
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Virology. 1992 Sep;190(1):176-83. doi: 10.1016/0042-6822(92)91203-7.
A ribozyme was constructed that specifically cleaves RNA that contains the first coding exon of the tat gene of HIV-1. This anti-tat ribozyme was incorporated into a Moloney murine leukemia virus vector. A sequence containing only the 48-nucleotide antisense region of the ribozyme was also inserted into the retroviral vector. Human T-cell lines constitutively producing the tat-antisense and the anti-tat ribozyme RNA were created by transduction into Jurkat cells. When challenged with HIV-1, both the tat-antisense and anti-tat ribozyme-producing cells inhibited the replication of HIV-1. The antisense vector conferred a greater resistance to HIV-1 replication than did the anti-tat ribozyme vector.
构建了一种核酶,它能特异性切割含有HIV-1 tat基因首个编码外显子的RNA。这种抗tat核酶被整合到莫洛尼鼠白血病病毒载体中。仅包含核酶48个核苷酸反义区域的序列也被插入到逆转录病毒载体中。通过转导进入Jurkat细胞,创建了组成性产生tat反义RNA和抗tat核酶RNA的人T细胞系。当用HIV-1攻击时,产生tat反义RNA和抗tat核酶的细胞均抑制了HIV-1的复制。反义载体赋予的对HIV-1复制的抗性比抗tat核酶载体更强。