Attenuation of Viruses by Large-Scale Recoding of their Genomes: the Selection Is Always Biased

Attenuation of Viruses by Large-Scale Recoding of their Genomes: the Selection Is Always Biased
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DOI:
10.1007/s40588-018-0080-3
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发表时间:
2018-03-01
影响因子:
5.2
通讯作者:
Kunec, Dusan
Kunec, Dusan
中科院分区:
其他
文献类型:
--
作者:
Osterrieder, Nikolaus;Kunec, Dusan

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综述目的:本文综述了病毒基因组大规模重组对病毒衰减的认识,并讨论了构建更好、更安全的改良活疫苗的最终必要条件。最近的研究结果表明,密码子和密码子对去优化是快速和可靠的方法,可用于开发减毒疫苗候选。通过大规模重新编码而减弱的病毒具有附加值,即它们在基因上非常稳定。然而,通过重新编码导致病毒衰减的确切机制尚未确定。摘要虽然大规模重新编码的优势(快速、简单、有效和普遍适用)已经知道十多年了,但这种方法还没有得到充分的探索,人们的注意力集中在数量有限的RNA病毒上。应探索通过大规模重新编码来减弱病毒,以对抗已知和未来的病毒威胁。
Purpose of Review This review summarizes the current understanding of virus attenuation by large-scale recoding of viral genomes and discusses what would ultimately be necessary for construction of better and safer live modified virus vaccines.Recent Findings It has been shown that codon and codon pair deoptimization are rapid and robust methods that can be used for the development of attenuated vaccine candidates. The viruses attenuated by large-scale recoding have the added value that they are extremely genetically stable. However, the exact mechanisms that lead to viral attenuation by recoding are yet to be determined.Summary While the advantages of large-scale recoding (speed, simplicity, potency, and universal applicability) have been known for more than a decade, this approach has been only inadequately explored and the attention was focused on a limited number of RNA viruses. Attenuation of viruses by large-scale recoding should be explored to combat known and future viral threats.