ABSTRACT
Targeted drug delivery is highly desirable in the clinic. But development of a robust, yet safe systemic delivery platform, avoidance of undesirable side-effects resulting from accumulation in healthy organs and exhibiting high therapeutic efficacy has been far from what is needed for successful clinical translation. RNA nanotechnology has emerged as a versatile platform for fabricating RNA-based modalities with tunable physiochemical properties and favorable pharmacological profiles in tumor-bearing mice. The lead candidate in RNA nanotechnology frontier is based on the packaging RNA derived from bacteriophage phi29 DNA packaging motor. The packaging RNA motif has emerged as an adaptable scaffold for fabricating RNA nanoparticles with targeting and therapeutic modules that exhibit favorable pharmacological properties in cancer mouse models. The intrinsic property of RNA as a nanomaterial is particularly attractive for delivering RNA-based drugs. Herein, we review how packaging RNA-based nanoparticles can overcome critical barriers in targeted drug delivery arena and discuss prospects for further development as a clinical modality in cancer therapy.
