کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6486677 | 1416259 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Amino acid misincorporation in recombinant proteins
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Proteins provide the molecular basis for cellular structure, catalytic activity, signal transduction, and molecular transport in biological systems. Recombinant protein expression is widely used to prepare and manufacture novel proteins that serve as the foundation of many biopharmaceutical products. However, protein translation bioprocesses are inherently prone to low-level errors. These sequence variants caused by amino acid misincorporation have been observed in both native and recombinant proteins. Protein sequence variants impact product quality, and their presence can be exacerbated through cellular stress, overexpression, and nutrient starvation. Therefore, the cell line selection process, which is used in the biopharmaceutical industry, is not only directed towards maximizing productivity, but also focuses on selecting clones which yield low sequence variant levels, thereby proactively avoiding potentially inauspicious patient safety and efficacy outcomes. Here, we summarize a number of hallmark studies aimed at understanding the mechanisms of amino acid misincorporation, as well as exacerbating factors, and mitigation strategies. We also describe key advances in analytical technologies in the identification and quantification of sequence variants, and some practical considerations when using LC-MS/MS for detecting sequence variants.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biotechnology Advances - Volume 36, Issue 1, JanuaryâFebruary 2018, Pages 168-181
Journal: Biotechnology Advances - Volume 36, Issue 1, JanuaryâFebruary 2018, Pages 168-181
نویسندگان
H. Edward Wong, Chung-Jr Huang, Zhongqi Zhang,