Synthetic Biology

Controls for a synthetic RNA circuit

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Science  16 Nov 2018:
Vol. 362, Issue 6416, pp. 789-790
DOI: 10.1126/science.362.6416.789-d

Gene therapy generally relies on delivering DNA into cells along with strategies to control its expression. Synthetic messenger RNA (mRNA) is an attractive alternative gene therapy vehicle for applications that require transient protein expression, but controlling this expression remains challenging. One approach is to add a degradation domain to the protein, but this may compromise its proper function. Wagner et al. engineered small-molecule-responsive RNA binding proteins (RBPs) to control expression of proteins from synthetic mRNA. By regulating binding of the RBPs, they can regulate the timing and magnitude of expression of reporter proteins in engineered circuits that use either synthetic RNAs with base modifications (modRNA) designed to decrease immunogenicity or self-replicating RNAs (replicons) that give high levels of expression.

Nat. Chem. Biol. 14, 1043 (2018).

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