密码子使用偏好性
免疫原性
计算生物学
核酸
生物
功能(生物学)
基因
遗传学
基因组
免疫系统
作者
Vincent P. Mauro,Stephen A. Chappell
标识
DOI:10.1016/j.molmed.2014.09.003
摘要
Codon optimization describes gene engineering approaches that use synonymous codon changes to increase protein production. Applications for codon optimization include recombinant protein drugs and nucleic acid therapies, including gene therapy, mRNA therapy, and DNA/RNA vaccines. However, recent reports indicate that codon optimization can affect protein conformation and function, increase immunogenicity, and reduce efficacy. We critically review this subject, identifying additional potential hazards including some unique to nucleic acid therapies. This analysis highlights the evolved complexity of codon usage and challenges the scientific bases for codon optimization. Consequently, codon optimization may not provide the optimal strategy for increasing protein production and may decrease the safety and efficacy of biotech therapeutics. We suggest that the use of this approach is reconsidered, particularly for in vivo applications.
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