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Using TRIM5α as an HIV therapeutic: The alpha gene?

机译:使用TRIM5α作为HIV治疗剂:α基因?

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Introduction: As HIV continues to spread worldwide, new therapies which have the potential to treat and cure infected patients need to be developed. The results observed with the "Berlin patient" who received a bone marrow transplant with HIV-resistant hematopoietic stem cells highlight the potential of HIV gene therapy to be used as an alternative treatment. With the discovery of TRIM5α, an HIV inhibitor and species-specific restriction factor, a new molecule can be evaluated as an HIV gene therapeutic. Nonhuman primate TRIM5α orthologs restrict HIV infection, whereas human TRIM5α does not. However, upon genetic modification, variations to human TRIM5α have been made which are capable of potent HIV restriction. Areas covered: This review seeks to cover the discovery and biology of various HIV-restrictive nonhuman primate TRIM5α orthologs, modifications made to human TRIM5α to enable HIV restriction, and the use of these molecules in an HIV gene therapy setting. Expert opinion: Engineered human TRIM5α molecules, demonstrated to be strong inhibitors of HIV infection, have the potential of being used as new HIV therapeutics in human gene therapy clinical trials. By combining TRIM5α with other highly potent anti-HIV molecules, the generation of an HIV-resistant immune system and potential cure for infected patients may be accomplished.
机译:简介:随着艾滋病毒继续在世界范围内传播,需要开发具有治疗和治愈感染患者潜力的新疗法。在接受“抗艾滋病毒”的造血干细胞骨髓移植的“柏林病人”中观察到的结果凸显了艾滋病毒基因治疗被用作替代治疗的潜力。随着TRIM5α(一种HIV抑制剂和物种特异性限制因子)的发现,一种新分子可以被评估为HIV基因治疗剂。非人类灵长类动物TRIM5α直系同源物限制HIV感染,而人类TRIM5α则没有。然而,经过基因修饰,已经对人TRIM5α进行了变异,其能够有效地限制HIV。涵盖领域:本综述旨在涵盖各种对HIV限制性非人类灵长类TRIM5α直系同源物的发现和生物学,对人类TRIM5α的修饰以实现对HIV的限制,以及这些分子在HIV基因治疗中的用途。专家意见:工程人类TRIM5α分子被证明是HIV感染的强抑制剂,有潜力在人类基因治疗临床试验中用作新型HIV治疗剂。通过将TRIM5α与其他高效抗HIV分子结合,可以实现HIV抗性免疫系统的产生和对感染患者的潜在治愈。

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