형질전환 식물세포배양을 이용한 바이오의약품 생산
Production of biopharmaceuticals in transgenic plant cell suspension cultures
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형질전환 식물세포 배양은 동물유래 바이러스로부터 안전하며 그에 따라 정제비용을 절감할 수 있으며, 값싼 배지가격으로 고가의 바이오의약 단백질의 대체생산 시 스템으로 각광받고 있다. 하지만 식물 고유의 당쇄화 유 형과 기존 생산시스템에 비해 낮은 생산성으로 인해 아 직까지 허가된 사례가 없는 실정이다. 이를 해결해기 위 해 중점적으로 수행되어야 할 분야로는 PMP 당쇄의 인 간화와 낮은 생산성을 극복하기 위한 강력한 프로모터 의 개발을 들 수 있다. 또한 고부가가치의 바이오의약 단백질 시장에서 식물세포 대량배양 및 상업화를 위해 서는 bioreactor 배양 및 공장의 설립이 필수적이기 때문 에, 식물세포에 적합한 bioreactor의 종류를 선정하여 최 적의 공정을 개발하는 것이 중요하다. 또한 식물세포 bioreactor 배양에서 고려사항들에 대한 총체적인 이해가 필요하며, 공정 및 배지최적화를 통해 생산성 증대와 재 현성 있는 생산시스템의 확립이 가능할 것이다. 근 미래 에 바이오의약 단백질 시장의 새로운 생산시스템으로서 한 축을 담당할 수 있을 것으로 사료된다.
Abstract
Transgenic plant cell cultures for the production of biopharmaceuticals including monoclonal antibodies, recombinant proteins have been regarded as an alternative platform in addition to traditional microbial fermentation and mammalian cell cultures. Plant-made pharmaceuticals (PMPs) have several advantages such as safety, cost-effectiveness, scalability and possibility of complex post-translational modifications. Increasing demand for the quantity and diversity of pharmaceutical proteins may accelerate the industrialization of PMP technology. Up to date, there is no plant-made recombinant protein approved by USFDA (Food and Drug Administration) for human therapeutic uses due to the technological bottlenecks of low expression level and slight differences in glycosylation. Regarding expression levels, it is possible to improve the productivity by using stronger promoter and optimizing culture processes. In terms of glycosylation, humanization has been attempted in many ways to reduce immune responses and to enhance the efficacy as well as stability. In this review article, all these respects of transgenic plant cell cultures were summarized. In addition, we also discuss the general characteristics of plant cell suspension cultures related with bioreactor design and operation to achieve high productivity in large scale which could be a key to successful commercialization of PMPs.
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