DUAL-TARGET INHIBITION OF HIV-1 INVITRO BY MEANS OF AN ADENOASSOCIATED VIRUS ANTISENSE VECTOR
DUAL-TARGET INHIBITION OF HIV-1 INVITRO BY MEANS OF AN ADENOASSOCIATED VIRUS ANTISENSE VECTOR
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DOI：
10.1126/science.1359646
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发表时间：
1992-11-27
期刊：
影响因子：
56.9
通讯作者：
WONG, KK
中科院分区：
文献类型：
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作者：
CHATTERJEE, S;JOHNSON, PR;WONG, KK
用腺相关病毒载体介导的反义RNA介导人造血细胞和非造血细胞对人类免疫缺陷病毒1型（HIV-1）的细胞内耐药性。反义靶点存在于所有HIV-1转录物中，包括TAR序列和多聚腺苷酸化信号，TAR序列对转录和病毒复制至关重要。表达反义RNA的细胞系对HIV-1长末端重复序列指导的基因表达的抑制率高达95%，感染性HIV-1产生的减少率超过99%，没有可检测到的细胞毒性。由于腺相关病毒载体的高效转录和不能与HIV-1重组，腺相关病毒载体代表了一种有前途的抗逆转录病毒基因治疗形式。
An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy.