Therapeutic applications of RNA nanostructures

RNA-based therapeutics have gained wide public interest in recent years. RNA is a versatile molecule that exists in many forms including mRNA, siRNA, miRNA, ribozymes, and other non-coding RNAs and is primarily applied for gene therapy. RNA is also used as a modular building block to construct RNA nanostructures. The programmable nature of RNA nanostructures enables the generation of simple, modulable, and multi-functional RNA-based therapeutics. Although the therapeutic application of RNA may be limited due to its structural instability, advances in RNA nanotechnology have improved the stability of RNA nanostructures for greater application. Various strategies have been developed to enhance the stability of RNA nanostructures enabling their application in vivo. In this review, we examine the therapeutic applications of RNA nanostructures. Non-immunogenic RNA nanostructures can be rationally designed with functional RNA molecules to modulate gene expression for gene therapy. On the other hand, nucleic acids can be sensed by cellular receptors to elicit an innate immune response, for which certain DNA and RNA motifs can function as adjuvants. Taking advantage of this adjuvant potential, RNA nanostructures can be used for immunotherapy and be designed for cancer vaccines. Thus, we examine the therapeutic application of immunogenic RNA nanostructures for cancer immunotherapy. RNA nanostructures represent promising platforms to design new nanodrugs, gene therapeutics, immunotherapeutic adjuvants, and cancer vaccines. Ongoing research in the field of RNA nanotechnology will continue to empower the development of RNA nanostructure-based therapeutics with high efficacy and limited toxicity. Non-immunogenic RNA nanostructures are functionalized for/with RNAi, mRNA, ribozymes, CRISPR, and small molecule drugs. Immunogenic RNA nanostructures are designed as immunostimulants and cancer vaccine platforms. Created in Biorender.com.