화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.137, No.32, 10268-10275, 2015
In Vitro Reversible Translation Control Using gamma PNA Probes
On-demand regulation of gene expression in living cells is a central goal of chemical biology and antisense therapeutic development. While significant advances have allowed regulatory modulation through inserted genetic elements, on-demand control of the expression/translation state of a given native gene by complementary sequence interactions remains a technical challenge. Toward this objective, we demonstrate the reversible suppression of a luciferase gene in cell-free translation using Watson Crick base pairing between the mRNA and a complementary gamma-modified peptide nucleic acid (gamma PNA) sequence with a noncomplementary toehold. Exploiting the favorable thermodynamics of gamma PNA-gamma PNA interactions, the antisense sequence can be removed by hybridization of a second, fully complementary gamma PNA, through a strand displacement reaction, allowing translation to proceed. Complementary RNA is also shown to displace the bound antisense gamma PNA, opening up possibilities of in vivo regulation by native gene expression.