Ribozymes in gene therapy of HIV-1
Ribozymes in gene therapy of HIV-1
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DOI：
10.2741/macpherson
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发表时间：
1999-06-01
期刊：
影响因子：
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通讯作者：
Symonds, Geoff P.
中科院分区：
文献类型：
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作者：
MacPherson, Janet L.;Ely, Julie A.;Symonds, Geoff P.
人类免疫缺陷病毒1型（HIV-1）是获得性免疫缺陷综合征（AIDS）的主要病原体。HIV-1是一种慢病毒，是逆转录病毒科的一个独立属，是整合到宿主细胞基因组中并在细胞内复制的复杂RNA病毒。核酶是具有酶样切割特性的催化RNA分子，其可以被设计为靶向HIV-1基因组内的特定RNA序列。除了基因组RNA之外，几种RNA中间体，包括剪接变体，可以被单个核酶靶向。我们和其他人已经证明了核酶在各种培养细胞中抑制HIV-1复制的能力。用于HIV-1感染的核酶基因治疗是一种治疗方法，其提供了优于常规治疗的几个潜在优势，因为它可以潜在地影响病毒载量和免疫系统的恢复。核酶基因治疗可用作化疗药物的辅助，实现病毒抑制，并促进免疫恢复，而没有患者依从性的问题。目前，抗HIV-1核酶正在两个独立的I期临床试验中进行测试。
Human immunodeficiency virus type 1 (HIV-1) is the primary etiologic agent for Acquired Immune Deficiency Syndrome (AIDS). HIV-1 is a lentivirus, a separate genus of the Retroviridae, which are complex RNA viruses that integrate into the genome of host cells and replicate intracellularly. Ribozymes are catalytic RNA molecules with enzyme-like cleavage properties, that can be designed to target specific RNA sequences within the HIV-1 genome. In addition to the genomic RNA, several RNA intermediates, including splice variants, can be targeted by a single ribozyme. We and others have demonstrated the ability of ribozymes to suppress HIV-1 replication in a variety of cultured cells. Ribozyme gene therapy for HIV-1 infection is a therapeutic approach that offers several potential advantages over conventional therapies in that it can potentially impact on both viral load and restoration of the immune system. Ribozyme gene therapy may be used as an adjunct to chemotherapeutic drugs, effecting viral suppression, and facilitating immune restoration without problems of patient compliance. Currently, an anti-HIV-1 ribozyme is being tested in two separate Phase I Clinical Trials.