Control of alphavirus-based gene expression using engineered riboswitches.
Virology
; 483: 302-11, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26005949
ABSTRACT
Alphavirus-based replicons are a promising nucleic acid vaccine platform characterized by robust gene expression and immune responses. To further explore their use in vaccination, replicons were engineered to allow conditional control over their gene expression. Riboswitches, comprising a ribozyme actuator and RNA aptamer sensor, were engineered into the replicon 3' UTR. Binding of ligand to aptamer modulates ribozyme activity and, therefore, gene expression. Expression from DNA-launched and VRP-packaged replicons containing riboswitches was successfully regulated, achieving a 47-fold change in expression and modulation of the resulting type I interferon response. Moreover, we developed a novel control architecture where riboswitches were integrated into the 3' and 5' UTR of the subgenomic RNA region of the TC-83 virus, leading to an 1160-fold regulation of viral replication. Our studies demonstrate that the use of riboswitches for control of RNA replicon expression and viral replication holds promise for development of novel and safer vaccination strategies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Virologia
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Regulação Viral da Expressão Gênica
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Alphavirus
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Aptâmeros de Nucleotídeos
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Riboswitch
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Biologia Molecular
Idioma:
En
Revista:
Virology
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos