Aptamer-Array-Guided Protein Assembly Enhances Synthetic mRNA Switch Performance

Synthetic messenger RNA (mRNA) switches are powerful synthetic biological tools that can sense cellular molecules to manipulate cell fate. However, their performances are limited by high output signal noise due to leaky output protein expression. Here, we designed a readout control module that disables protein leakage from generating signal. Aptamer array on the switch guides the inactive output protein to self-assemble into functional assemblies that generate output signal. Leaky protein expression fails to saturate the array, thus produces marginal signal. In this study, we demonstrated that switches with this module exhibit substantially lower signal noise and, consequently, higher input sensitivity and wider output range. Such switches are applicable for different types of input molecules and output proteins. The work here demonstrates a new type of spatially guided protein self-assembly, affording novel synthetic mRNA switches that promise accurate cell manipulation for biomedical applications.

Automated summary

This study introduces a readout control module that reduces protein leakage in synthetic mRNA switches, thereby decreasing signal noise and increasing input sensitivity and output range. These switches are applicable to different types of input molecules and output proteins, offering potential for accurate cell manipulation in biomedical applications.