Construction of a Live-Attenuated HIV-1 Vaccine through Genetic Code Expansion

被引:64
作者
Wang, Nanxi [1 ]
Li, Yue [2 ,3 ]
Niu, Wei [1 ]
Sun, Ming [2 ,3 ]
Cerny, Ronald [1 ]
Li, Qingsheng [2 ,3 ]
Guo, Jiantao [1 ]
机构
[1] Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA
[2] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA
[3] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA
关键词
attenuated vaccine; genetic code expansion; HIV-1; vaccine; unnatural amino acid; virus engineering; UNNATURAL AMINO-ACIDS; MAMMALIAN-CELLS; PLASMA-MEMBRANE; PROTEINS; SYSTEM; VIRUS; AIDS;
D O I
10.1002/anie.201402092
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off invitro.
引用
收藏
页码:4867 / 4871
页数:5
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