人类治疗中密码子优化的批判性分析。
A critical analysis of codon optimization in human therapeutics.
作者信息
Mauro Vincent P, Chappell Stephen A
机构信息
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Trends Mol Med. 2014 Nov;20(11):604-13. doi: 10.1016/j.molmed.2014.09.003. Epub 2014 Sep 25.
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.
密码子优化描述了利用同义密码子变化来提高蛋白质产量的基因工程方法。密码子优化的应用包括重组蛋白药物和核酸疗法，如基因疗法、mRNA疗法和DNA/RNA疫苗。然而，最近的报告表明，密码子优化可能会影响蛋白质的构象和功能，增加免疫原性，并降低疗效。我们对这一主题进行了批判性回顾，确定了其他潜在风险，包括一些核酸疗法特有的风险。该分析突出了密码子使用的复杂性不断演变，并对密码子优化的科学依据提出了挑战。因此，密码子优化可能不是提高蛋白质产量的最佳策略，可能会降低生物技术疗法的安全性和疗效。我们建议重新考虑这种方法的使用，特别是在体内应用方面。
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