Engineering programmable RNA synthetic circuits in mammalian cells

The ability to reprogram mammalian cells with tight spatiotemporal control over gene expression and cell response has provided a powerful means to address biomedical challenges. To provide safer synthetic biology products, RNA has recently emerged as an alternative to DNA to deliver transgenes into mammalian cells. In this review, we discuss recent tools implemented to engineer programmable RNA-based synthetic circuits in mammalian cells. We examine the limitations of RNA-encoded gene delivery, and we highlight significant studies that successfully improved payloads expression and persistence and maximized RNA delivery efficiency. Finally, we conclude by discussing examples of RNA-based therapeutics and future perspectives.