Human Protein Process Sciences, Lille, France.
Vox Sang. 2011 Jan;100(1):68-83. doi: 10.1111/j.1423-0410.2010.01384.x.
For almost 50 years, the fractionation of human plasma has been the sole possible source of a wide range of therapeutic proteins--such as coagulation factors, anticoagulants, immunoglobulins, and albumin--essential to the treatment of serious congenital or acquired bleeding or immunological diseases. In the last 20 years, the application of recombinant technologies to mammalian cell cultures has made possible--although with some limitations in productivity, costs, and immunogenic risks--to produce and commercialize complex plasma glycoproteins for human therapeutic applications and has opened the way to the development of new molecular entities. Today, the advanced exploration of alternative cell lines and enhanced cell culture systems, as well as the development of alternative expression technologies, such as transgenic animals, is opening a new era in the production of the full range of recombinant plasma protein therapeutics. In this review, we examine the achievements and ongoing challenges of the recombinant DNA technology as a platform for the production of plasma proteins and the advantages and limitations of such products compared to fractionated plasma proteins.
近 50 年来，人血浆的分离一直是广泛的治疗性蛋白质（如凝血因子、抗凝剂、免疫球蛋白和白蛋白）的唯一可能来源，这些蛋白质对于治疗严重的先天性或获得性出血或免疫性疾病至关重要。在过去的 20 年中，重组技术在哺乳动物细胞培养中的应用已经使得（尽管在生产力、成本和免疫原性风险方面存在一些限制）能够生产和商业化用于人类治疗应用的复杂血浆糖蛋白，并为开发新的分子实体开辟了道路。如今，对替代细胞系和改良细胞培养系统的深入探索，以及替代表达技术（如转基因动物）的开发，正在开启生产全范围重组血浆蛋白治疗药物的新时代。在这篇综述中，我们研究了重组 DNA 技术作为生产血浆蛋白的平台的成就和持续挑战，以及与分离的血浆蛋白相比，此类产品的优势和局限性。
