Kravatsky Y V, Chechetkin V R, Fedoseeva D M, Gorbacheva M A, Kretova O V, Tchurikov N A
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
Mol Biol (Mosk). 2016 May-Jun;50(3):480-5. doi: 10.7868/S0026898416020117.
The development of gene-therapy technology using RNAi for AIDS/HIV-1 treatment is a prospective alternative to traditional anti-retroviral therapy. RNAi targets could be selected in HIV-1 transcripts and in CCR5 mRNA. Previously, we experimentally selected a number of efficient siRNAs that target HIV-1 RNAs. The viral genome mutates frequently, and RNAi strength is very sensitive, even for a single mismatches. That is why it is important to study nucleotide sequences of targets in clinical isolates of HIV-1. In the present study, we analyzed mutations in 6 of about 300-bp regions containing RNAi targets from HIV-1 subtype A isolates in Russia. Estimates of the mean frequencies of mutations in the targets were obtained and the frequencies of mutations in the different codon positions were compared. The frequencies of mutations in the vicinity of the targets and directly within the targets were also compared and have been shown to be approximately the same. The frequencies of indels in the chosen regions have been assessed. Their frequencies have proved to be two to three orders of magnitude less compared to that for mutations.
利用RNA干扰技术进行艾滋病/ HIV - 1治疗的基因治疗技术的发展是传统抗逆转录病毒疗法的一种前瞻性替代方案。RNA干扰靶点可在HIV - 1转录本和CCR5 mRNA中选择。此前，我们通过实验筛选出了一些靶向HIV - 1 RNA的高效小干扰RNA（siRNA）。病毒基因组频繁突变，而且RNA干扰强度非常敏感，即使只有一个错配。这就是为什么研究HIV - 1临床分离株中靶点的核苷酸序列很重要。在本研究中，我们分析了来自俄罗斯的HIV - 1 A亚型分离株中约300个碱基对区域（包含RNA干扰靶点）中的6个区域的突变情况。获得了靶点突变平均频率的估计值，并比较了不同密码子位置的突变频率。还比较了靶点附近和靶点内的突变频率，结果显示二者大致相同。评估了所选区域的插入缺失频率。结果证明，与突变频率相比，其频率低两到三个数量级。
