Zhu Jingen, Tao Pan, Mahalingam Marthandan, Rao Venigalla B
Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Bio Protoc. 2020 Apr 5;10(7):e3573. doi: 10.21769/BioProtoc.3573.
A viral vector that can safely and efficiently deliver large and diverse molecular cargos into cells is the holy grail of curing many human diseases. Adeno-associated virus (AAV) has been extensively used but has a very small capacity. The prokaryotic virus T4 has a large capacity but lacks natural mechanisms to enter mammalian cells. Here, we created a hybrid vector by combining T4 and AAV into one nanoparticle that possesses the advantages of both. The small 25 nm AAV particles are attached to the large 120 nm x 86 nm T4 head through avidin-biotin cross-bridges using the phage decoration proteins Soc (small outer capsid protein) and Hoc (highly antigenic outer capsid protein). AAV thus "piggy-backed" on T4 capsid, by virtue of its natural ability to enter many types of human cells efficiently acts as a "driver" to deliver large cargos associated with the T4 head. This unique T4-AAV hybrid vector approach could pave the way for the development of novel therapeutics in the future.
一种能够安全、高效地将大量不同分子货物递送至细胞内的病毒载体是治愈许多人类疾病的圣杯。腺相关病毒（AAV）已被广泛使用，但其容量非常小。原核病毒T4容量大，但缺乏进入哺乳动物细胞的天然机制。在此，我们通过将T4和AAV组合成一个纳米颗粒创建了一种杂交载体，该纳米颗粒兼具两者的优点。利用噬菌体装饰蛋白Soc（小外衣壳蛋白）和Hoc（高度抗原性外衣壳蛋白），通过抗生物素蛋白-生物素交联桥，25纳米的小AAV颗粒附着在120纳米×86纳米的大T4头部。AAV因此“搭载”在T4衣壳上，凭借其有效进入多种人类细胞的天然能力，充当“驱动者”来递送与T4头部相关的大量货物。这种独特的T4-AAV杂交载体方法可能为未来新型疗法的开发铺平道路。
