Abstract

This attractive and intriguing Ribonucleic acid (RNA) nanotechnology has been conceptualized over the last two decades and with our increasing understanding of RNA structure and function and improvements of RNA nanotechnology it is now possible to use this in clinical settings. Here we review the unique properties and the recent advances in RNA nanotechnology and then look at its scientific and preclinical applications for tumor diagnosis and targeted delivery and RNA-based therapy using RNA nanoparticles with diverse structures and functions. Finally, we discuss the future perspectives and challenges to RNA nanotechnology. RNA can be designed and manipulated in a similar way to DNA while having different rules for base-pairing and displaying functions similar to proteins. Rationally designed RNA nanoparticles based on the three-way junction (3WJ) motif as the core scaffold have been extensively explored in the field of nanomedicine and targeted cancer diagnosis and therapy. RNA nanostructures based on 3WJs demonstrate promising future applications due to their thermal stability, molecular-level plasticity, multifunctional chemotherapeutic drug delivery and other intrinsic characteristics, which will greatly improve the treatment of cancer and promote further major breakthroughs in this field.

Highlights

  • Ribonucleic acid (RNA) nanotechnology is an emerging field because RNA can be used as a unique polymeric material to construct a variety of nanostructures, such as nanoparticles, bundles, membranes, and polygons [1]

  • These studies have given a tremendous boost to the progress of RNA nanotechnology and currently, the concept of RNA nanotechnology is defined as a specific research field for the design, processing, fabrication, and application of RNA nanoparticles

  • Incorporation of RNA aptamers to packaging RNAs (pRNA)-3WJ nanoparticles, where functional sequences are fused into core strands without affecting their original folding, has helped aptamers internalize into cancer cells via receptor-mediated endocytosis and this lowers the off-target effect of the RNA nanoparticles [75]

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Summary

Introduction

Ribonucleic acid (RNA) nanotechnology is an emerging field because RNA can be used as a unique polymeric material to construct a variety of nanostructures, such as nanoparticles, bundles, membranes, and polygons [1]. Catalytic domains and DNA packaging units which play vital roles in genetic and metabolic processes, can be used as building modules individually, or simultaneously conjugated to the core scaffold to achieve their physiological functions. These well-known biological RNA motifs can be spliced and assembled with synthetic RNA fragments to enable those structures to possess more complex and diverse functions [8]. The inherent complementary interaction of genetic translational mechanisms between RNA and DNA leads to the hybridization of DNA and RNA molecules naturally, which plays a synergistic role between DNA with relative structural stability and RNA with abundant chemical diversity enabling nanostructure design with different functions [9]

The origin of RNA nanotechnology
Uniqueness of RNA nanotechnology
The structure of phi29 pRNA-3WJs
Construction of RNA nanoparticles based on pRNA-3WJs
RNA nanoparticles with different sizes
RNA nanoparticles with different shapes
Non-invasive cancer detection
Specific drug targeting strategies
Guiding cancer cell differentiation
Immunotherapy for cancer
Challenges and solutions for the application of RNA nanotechnology
RNA instability
Thermodynamic instability
Toxicity and side effects
Complexity of RNA structures

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