Using phytoglycogen to deliver long dsRNA molecules as an antiviral drug in shrimp

按价值计算，虾是世界上最大的单一海鲜商品，2017年估计价值400亿美元。水产养殖对虾产量主要由两个物种主导，即黑虎虾(斑节对虾)和太平洋白虾(南美白对虾)。这两个物种都非常容易受到病毒疾病爆发的影响，通常灾难性的大规模死亡率从80%到100%不等。对虾的抗病毒免疫反应尚不完全清楚；然而，我们确实知道双链(DS)RNA，无论是否编码针对感染的病毒序列，都可以提供保护，防止病毒复制。本研究将使用我们的工业合作伙伴(Glysantis Inc；Guelph，On)开发的一种新型植物糖原(PHG)纳米颗粒作为dsRNA的载体，将其用作虾饲料添加剂。PHG是一种无毒、食品级、可生物降解、无免疫原性、高度可化学修饰的纳米粒子，在这一应用中具有很大的吸引力。在初步研究中，我们已经证明，与单独使用dsRNA相比，用dsRNA-PHG处理的水生动物细胞可以更有力地(&gt；10倍)诱导天生的抗病毒基因。因此，使用dsRNA-PHG将减少保护虾所需的dsRNA的数量，从而降低成本。除了这些发现的市场价值外，这项研究还将拓宽我们对dsRNA介导的对虾抗病毒途径的理解，并建立一个连续的对虾细胞系，用于开发诊断工具和对虾免疫的基础研究。将这些知识结合在一起，将大大提高我们对虾的先天抗病毒免疫力的理解，从而改善这种重要的经济动物，并对加拿大公司产生积极影响，产生新的收入来源和就业机会。

Shrimp is the largest single seafood commodity by value in the world, estimated at $40 billion in 2017. Aquaculture shrimp production is dominated by two species, the black tiger shrimp (Penaeus monodon) and the pacific white shrimp (Penaeus vannamei). Both of these species are exquisitely susceptible to outbreaks of viral disease, generally with catastrophic mass mortalities ranging from 80-100%. The antiviral immune response in shrimp is not fully understood; however, we do know that double-stranded (ds)RNA, whether coding for virus sequences specific to the infection or not can lend protection against virus replication. The present study will use a novel phytoglycogen (PhG) nanoparticle, developed by our industrial partner (Glysantis Inc; Guelph, ON) as a carrier for dsRNA to be used as a shrimp feed additive. PhG is attractive as a nanoparticle in this application because it is non-toxic, food-grade, biodegradable, non-immunogenic, and highly amenable to chemical modifications. In preliminary studies we have demonstrated that aquatic animal cells treated with dsRNA-PhG mounted a more robust (>10 fold) induction of innate antiviral genes when compared to dsRNA alone. Thus using dsRNA-PhG would reduce the amount of dsRNA needed to protect shrimp, thus reducing cost. In addition to the marketability of these findings, this research will also broaden our understanding of dsRNA-mediated antiviral pathways in shrimp and generate a continuous shrimp cell line for the development of diagnostic tools, and basic research on shrimp immunity. Combined this knowledge will significantly progress our understanding of shrimp innate antiviral immunity, for the betterment of this economically important animal, as well as positively impact a Canadian company, producing novel revenue streams and employment opportunities.