Rouf S A, Moo-Young M, Chisti Y
Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Biotechnol Adv. 1996;14(3):239-66. doi: 10.1016/0734-9750(96)00019-5.
Plasminogen activators have immense clinical significance as thrombolytic agents for management of stroke and myocardial infarction. Tissue-type plasminogen activator (tPA) is generally preferred as being effective and safer than either urokinase or streptokinase type activators. Large-scale production of tPA became possible through groundbreaking developments in cell lines and bioprocess technology. Nevertheless, at thousands of dollars per treatment, tPA remains expensive. Enhancing cellular productivity and downstream product recovery through new approaches continue to be major challenges as discussed in this review. Recent clinical experience suggests the need for yet better fibrinolytic agents and attempts are underway to modify the tPA molecule to second generation products. Emerging trends in this field are outlined.
纤溶酶原激活剂作为治疗中风和心肌梗死的溶栓药物具有巨大的临床意义。组织型纤溶酶原激活剂(tPA)通常更受青睐,因为它比尿激酶或链激酶型激活剂更有效、更安全。通过细胞系和生物工艺技术的突破性发展,tPA的大规模生产成为可能。然而,tPA每次治疗费用高达数千美元,仍然昂贵。如本综述所讨论的,通过新方法提高细胞生产力和下游产物回收率仍然是主要挑战。最近的临床经验表明需要更好的纤溶药物,目前正在尝试将tPA分子改性为第二代产品。本文概述了该领域的新趋势。