Self-assembled DNA/RNA nanoparticles as a new generation of therapeutic nucleic acids: immunological compatibility and other translational considerations

Abstract Therapeutic nucleic acids (TNAs) are rapidly being embraced as effective interventions in a variety of genetic disorders, cancers, and viral/microbial infections, as well as for use in improving vaccine efficacy. Many traditional nucleotide-based formulations have been approved for clinical use, while various macromolecular nucleic acids are in different phases of preclinical and clinical development. Various nanotechnology carriers, including but not limited to liposomes, emulsions, dendrimers, and polyplexes, are considered for their improved delivery and reduced toxicity compared to traditional TNAs. Moreover, a new generation of TNAs has recently emerged and is represented by DNA/RNA nanoparticles formed by the self-assembly of DNA, RNA, or hybrid DNA-RNA oligonucleotides into 1D, 2D, and 3D structures of different shapes. In this mini-review, I will discuss immunocompatibility and other translational aspects in the development of this new class of promising nucleic acid therapeutics.