Predictive glycoengineering of biosimilars using a Markov chain glycosylation model
详细信息 查看全文
- 作者：Philipp N. Spahn ; Anders H. Hansen ; Stefan Kol ; Bjø ; rn G. Voldborg and Nathan E. Lewis
- 刊名：Biotechnology Journal
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：12
- 期：2
- 全文大小：2032K
- ISSN：1860-7314
文摘
Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safety and efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its biogenesis. This usually implies that costly and time-consuming experimentation is required for clone identification and optimization of biosimilar glycosylation. Here, a computational method that utilizes a Markov model of glycosylation to predict optimal glycoengineering strategies to obtain a specific glycosylation profile with desired properties is described. The approach uses a genetic algorithm to find the required quantities to perturb glycosylation reaction rates that lead to the best possible match with a given glycosylation profile. Furthermore, the approach can be used to identify cell lines and clones that will require minimal intervention while achieving a glycoprofile that is most similar to the desired profile. Thus, this approach can facilitate biosimilar design by providing computational glycoengineering guidelines that can be generated with a minimal time and cost.