Engineered RNA Devices for In Vivo Targeted Therapeutics via Advanced Delivery Systems

ABSTRACT Engineered RNA devices can identify disease‐specific markers and precisely regulate gene expression, which is of great significance to the development of precision medicine. Some studies are shifting the focus from systemic drug delivery to precise gene regulation. A series of targeted delivery technologies has achieved enrichment of RNA drugs in specific tissues/organs. However, the limited cellular selectivity of RNA remains a major obstacle to progress in this field. The cellular precise regulation still requires much improvement. In recent years, advances in synthetic biology have facilitated the development of various RNA devices capable of specifically recognizing intracellular transcripts, proteins, and microRNAs. Nevertheless, the application of these tools remains largely restricted to in vitro cell detection and cell fate manipulation, due to insufficient cross‐disciplinary collaboration. Therefore, given the advantages of advanced delivery technologies, combined with the RNA devices that enable precise regulation of gene expression at the cellular level, now is an opportune moment to integrate these RNA devices with state‐of‐the‐art delivery platforms. Such integration promises to enhance the efficacy of engineered RNA devices for precise in vivo targeted therapeutics. In this review, we highlight examples of the advances and current limitations of RNA devices, including toehold switches, microRNAs, and ADAR (adenosine deaminase acting on RNA) sensors for precision disease treatment via advanced delivery systems. These considerations are essential to develop strategies for the targeted therapeutic exploitation of RNA device‐based and delivery systems as a powerful programmable biological platform. Furthermore, we will assess the current maturity of RNA device technology and identify emerging innovation areas expected to drive significant future progress.