摘要
通过病毒在细胞质主动转运和抵制细胞的制约因子和先天免疫反应的机制,病毒已经进化到穿越细胞障碍和进入到细胞核。病毒源载体系统利用病毒的能力把遗传信息输送入细胞,基于HIV-1的HIV慢病毒载体的发现到现在已超过三十年,它已成为需要转基因的基因组插入的生物医学研究和基因治疗的工具。现在,慢病毒基因传递到干细胞、免疫系统细胞包括T细胞、肝细胞、和许多其他与治疗相关的细胞类型的有效性是公认的。伴随着核酸,HIV-1病毒体携带对感染的早期步骤是必不可少的酶工具。这种包装酶甚至是非病毒源的蛋白质的能力,揭示了利用HIV-1入侵细胞的新途径。基于早期的已表明包装外源蛋白到病毒颗粒作为Gag和GagPol多肽部分的研究结果,我们已经建立了为传递DNA转座酶和设计的核酸酶的慢病毒蛋白转运。这种传递基因组工程蛋白质的策略有利于在很短的时间内的达到高的酶活性,并可能会提高基因组编辑的安全性。利用慢病毒载体的全部潜能,掺合外源蛋白,可以结合DNA转座因子或结合“一体化”慢病毒载体的同源性定向修复的供体序列。在这里,我们简要地描述了可能会影响细胞内的病毒基因和蛋白传递的限制因素,回顾当前慢病毒颗粒作为基因工程工具包的载体的状态。
关键词: 蛋白转导,锌指核酸酶,DNA转座酶,基因治疗,慢病毒载体。
Current Gene Therapy
Title:Lentiviral Delivery of Proteins for Genome Engineering
Volume: 16 Issue: 3
Author(s): Yujia Cai, Jacob Giehm Mikkelsen
Affiliation:
关键词: 蛋白转导,锌指核酸酶,DNA转座酶,基因治疗,慢病毒载体。
摘要: Viruses have evolved to traverse cellular barriers and travel to the nucleus by mechanisms that involve active transport through the cytoplasm and viral quirks to resist cellular restriction factors and innate immune responses. Virus-derived vector systems exploit the capacity of viruses to ferry genetic information into cells, and now - more than three decades after the discovery of HIV - lentiviral vectors based on HIV-1 have become instrumental in biomedical research and gene therapies that require genomic insertion of transgenes. By now, the efficacy of lentiviral gene delivery to stem cells, cells of the immune system including T cells, hepatic cells, and many other therapeutically relevant cell types is well established. Along with nucleic acids, HIV-1 virions carry the enzymatic tools that are essential for early steps of infection. Such capacity to package enzymes, even proteins of nonviral origin, has unveiled new ways of exploiting cellular intrusion of HIV-1. Based on early findings demonstrating the packaging of heterologous proteins into virus particles as part of the Gag and GagPol polypeptides, we have established lentiviral protein transduction for delivery of DNA transposases and designer nucleases. This strategy for delivering genome-engineering proteins facilitates high enzymatic activity within a short time frame and may potentially improve the safety of genome editing. Exploiting the full potential of lentiviral vectors, incorporation of foreign protein can be combined with the delivery of DNA transposons or a donor sequence for homology-directed repair in so-called ‘all-in-one’ lentiviral vectors. Here, we briefly describe intracellular restrictions that may affect lentiviral gene and protein delivery and review the current status of lentiviral particles as carriers of tool kits for genome engineering.
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Yujia Cai, Jacob Giehm Mikkelsen , Lentiviral Delivery of Proteins for Genome Engineering, Current Gene Therapy 2016; 16 (3) . https://dx.doi.org/10.2174/1566523216666160527143702
DOI https://dx.doi.org/10.2174/1566523216666160527143702 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
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