CLOTTING FACTORS FROM FISH BLOOD FOR FIBRIN SEALANTS

本项目的目的是从鲑鱼血浆中创建一种安全有效的外科纤维蛋白封闭剂。数百万的大型鲑鱼由水产养殖业饲养，这些鱼的血浆提供了高度保守的凝血因子的创新和替代来源。鲑鱼材料的一个可能的健康优势是对哺乳动物感染因子的安全性。具体目标是;（1）从装框鲑鱼的血浆中提取、纯化和体外评估凝血酶和纤维蛋白原;（2）评估跨物种（鲑鱼-人）感染因子的可能风险;（3）确定鲑鱼材料的免疫原性;和（4）在动物模型中体内测试鲑鱼材料。将纯化鲑鱼凝血酶和纤维蛋白原，并在不同浓度和条件下进行体外试验。将对多批（>1000条鱼）鲑鱼血浆进行鲑鱼病毒筛查，发现的任何病毒都将在人类细胞系中进行鉴定和感染性测试。将在大鼠和家兔中评价免疫原性。将在大鼠、犬和猪模型中比较鲑鱼纤维蛋白封闭剂和市售（人源性）封闭剂的体内有效性。拟议的商业应用：来源于鲑鱼血浆的纤维蛋白密封剂可以提供对哺乳动物感染因子的安全性，以及优于哺乳动物材料的某些物理化学优势。美国市场超过4亿美元，除了军事用途。

The objective of this project is to create a safe, efficacious surgical fibrin sealant from salmon plasma. Millions of large salmon are reared by the aqua-culture industry, and the plasma from these fish offers an innovative and alternative source of highly conserved clotting factors. A likely health advantage of the salmon material is safety from mammalian infectious agents. Specific aims are; (1) to extract, purify, and evaluate in vitro, thrombin and fibrinogen from the plasma of framed salmon; (2) evaluate the possible risks of trans-species (salmon-human) infectious agents; (3) determine the immunogenic properties of the salmon material; and (4) test the salmon material in vivo in animal models. Salmon thrombin and fibrinogen will be purified, and tested in vitro at varying concentration and conditions. Lots (>1000 fish) of salmon plasma will be screened for salmon virus, and any virus found will e identified and tested for infectivity in human cell lines. Immunogenicity will be evaluated in both rats and rabbits. The in vivo efficacy of a salmon fibrin sealant and a commercial (human-derived" sealant will be compared in rat, dog, and swine models. PROPOSED COMMERCIAL APPLICATIONS: A fibrin sealant derived from salmon plasma could offer safety from mammalian infectious agents, and certain physical-chemical advantages over mammalian material. The U.S. market is over $400 million, in addition to military use.