Controlling Multicycle Replication of Live-Attenuated HIV-1 Using an Unnatural Genetic Switch

Zhe Yuan, Nanxi Wang, Guobin Kang, Wei Niu, Qingsheng Li, Jiantao Guo

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. We investigated a novel approach to address this problem by controlling live-attenuated HIV-1 replication through an unnatural genetic switch that was based on the amber suppression strategy. Here we report the construction of all-in-one live-attenuated HIV-1 mutants that contain genomic copy of the amber suppression system. This genetic modification resulted in viruses that were capable of multicycle replication in vitro and could be switched on and off using an unnatural amino acid as the cue. This stand-alone, replication-controllable attenuated HIV-1 virus represents an important step toward the generation of a safe and efficacious live-attenuated HIV-1 vaccine. The strategy reported in this work can be adopted for the development of other live-attenuated vaccines.

Original languageEnglish (US)
Pages (from-to)721-731
Number of pages11
JournalACS Synthetic Biology
Issue number4
StatePublished - Apr 21 2017


  • HIV-1 vaccine
  • genetic code
  • live-attenuated vaccine
  • unnatural amino acid
  • virus engineering

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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