一种原核-真核杂合病毒载体，可将大负荷的基因和蛋白质递送入人体细胞。
A prokaryotic-eukaryotic hybrid viral vector for delivery of large cargos of genes and proteins into human cells.
机构信息
Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
出版信息
Sci Adv. 2019 Aug 21;5(8):eaax0064. doi: 10.1126/sciadv.aax0064. eCollection 2019 Aug.
Development of safe and efficient nanoscale vehicles that can deliver large molecular cargos into human cells could transform future human therapies and personalized medicine. Here, we design a hybrid viral vector composed of a prokaryotic virus (bacteriophage T4) and a eukaryotic virus [adeno-associated virus (AAV)]. The small 25-nm AAV is attached to the large 120 nm × 86 nm T4 head through avidin-biotin cross-bridges using the phage decoration proteins Soc and Hoc. AAV "piggy-backed" on T4 capsid, by virtue of its natural ability to enter human cells acted as an efficient "driver," delivering the largest payloads of foreign DNA (up to 170 kb) and protein (up to 1025 molecules) reported to date, and elicited robust immune responses in mice against flu and plague pathogens and conferred complete protection against lethal pneumonic plague challenge. The T4-AAV represents a unique platform for assembly of natural building blocks into potential therapeutics against genetic and infectious diseases.
开发安全高效的纳米载体，使其能够将大分子量的载物递送入人体细胞，这将有望改变未来的人类疗法和个性化医疗。在这里，我们设计了一种由原核病毒（噬菌体 T4）和真核病毒（腺相关病毒（AAV））组成的混合病毒载体。小的 25nm AAV 通过噬菌体能与生物素结合的 Soc 和 Hoc 蛋白与较大的 120nm×86nm T4 头部连接。由于 AAV 进入人体细胞的天然能力，AAV 可“搭便车”于 T4 衣壳上，作为高效的“驱动蛋白”，传递迄今为止报道的最大的外源 DNA（高达 170kb）和蛋白（高达 1025 个分子），并在小鼠中引发针对流感和瘟疫病原体的强烈免疫反应，还可完全抵御致命性肺鼠疫的挑战。T4-AAV 为组装潜在的针对遗传和传染病的治疗药物提供了一个独特的平台。
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