English

The research team of Professor Cai Xiaoxiao from West China School of Stomatology, Sichuan University and State Key Laboratory of Oral Diseases fabricated a bioswitchable delivery system for microRNA therapeutics based on a tetrahedral DNA nanostructure. Their research was published in Nature Protocols. Associate researcher Songhang Li and Associate professor Taoran Tian are co-first authors, Professor Cai Xiaoxiao is the corresponding author. Sichuan University is the only accomplishment unit for this article.

Due to their capacity to regulate nearly all processes within the human body, microRNA (miRNA) regulators have garnered significant attention in the realm of nucleic acid drug development. Various delivery systems have been engineered to address the inherent limitations of miRNA regulators, such as instability. Nevertheless, potential concerns regarding biological safety, toxicity, and transfection rates restrict most miRNA therapeutics to preclinical stages. Therefore, creating an effective delivery system for miRNA therapeutics that offers high stability, excellent biocompatibility, and superior delivery efficacy remains a substantial challenge. 

By employing RNase H-sensitive sequences as a trigger mechanism, the study developed a tetrahedral framework nucleic acid-based bioswitchable delivery system (BDS) designed to precisely regulate the release of therapeutic microRNAs (miRNAs). The BDS enhances the stability of therapeutic miRNA during transport while providing excellent cell and tissue permeability. The BDS can be constructed through either one-pot or two-step methods. This innovative delivery system is poised to significantly expand the application potential of miRNAs due to their abundance and functional diversity, presenting promising prospects in intelligent biomaterials.

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https://www.nature.com/articles/s41596-024-01050-7