The biggest challenge of gene therapy is to ensure that it reaches the target cells and is inhibited from acting on unintended cells. This specificity can enable systemic delivery of the drug without risks from off-target effects. Designing such specific molecular switches has received much attention from bioengineers and synthetic biologists.

In a breakthrough study, scientists from MIT and Harvard University engineered a novel RNA-based gating system that can trigger the expression of transgenes and subsequent production of therapeutics. The study, published in Nature Biotechnology, reports an efficient design for future gene therapy.

By reading tissue-specific transcription profiles to identify target cells, the authors devised a specific homing strategy called eToeholds to prevent off-target effects. eToehold is an RNA module that regulates the translation of the reporter gene based on its interaction with specific trigger RNAs (tgRNAs) present in only specific cells.