Developing artificial cytoskeletons using RNA origami-based nanotubes

The cytoskeleton plays a fundamental role in maintaining cellular architecture, enabling intracellular transport, and facilitating mechanical responsiveness. Mimicking this intricate biological framework through synthetic means offers promising prospects for nanotechnology, synthetic biology, and therapeutic applications. Recent advances in nucleic acid nanotechnology have positioned RNA origami as a versatile and programmable scaffold for constructing nanoscale architectures. This review explores the emerging concept of engineering artificial cytoskeletons using RNA origami-based nanotubes. We discuss the unique structural and functional advantages of RNA over DNA, including its ability to fold co-transcriptionally, form complex tertiary interactions, and interface with cellular machinery. Key strategies for designing and assembling RNA nanotubes that mimic microtubules and actin filaments are explored, along with efforts to control their length, stiffness, and spatial arrangement. Furthermore, we highlight the potential for dynamic remodelling and responsiveness through ligand-binding motifs, ribozymes, and RNA-protein interactions. Applications in intracellular scaffolding, targeted cargo transport, and as platforms for synthetic cell development are also reviewed. While significant challenges remain, including in-vivo stability and efficient delivery, RNA origami offers a transformative toolkit for constructing programmable, biomimetic cytoskeletal networks. This review aims to provide a foundational understanding of the field and inspire future developments at the intersection of RNA nanotechnology and synthetic cell engineering.