The International Society of RNA Nanotechnology and Nanomedicine (ISRNN): The Present and Future of the Burgeoning Field

Abstract

The International Society of RNA Nanotechnology and Nanomedicine (ISRNN) hosts an annual meeting series focused on presenting the latest research achievements involving RNA-based therapeutics and strategies, aiming to expand their current biomedical applications while overcoming the remaining challenges of the burgeoning field of RNA nanotechnology. The most recent online meeting hosted a series of engaging talks and discussions from an international cohort of leading nanotechnologists that focused on RNA modifications and modulation, dynamic RNA structures, overcoming delivery limitations using a variety of innovative platforms and approaches, and addressing the newly explored potential for immunomodulation with programmable nucleic acid nanoparticles. In this Nano Focus, we summarize the main discussion points, conclusions, and future directions identified during this two-day webinar as well as more recent advances to highlight and to accelerate this exciting field.

Figure 1.

(A) Polyadenylated nuclear (PAN) RNA encoded by Kaposi’s sarcoma-associated herpesvirus with roles in viral infectivity and implications for structural RNA biology. (B) Operating at the interface between computational and experimental RNA biology: characterization of RNA oxidation effects through engineered binding enhancement. Deposition of RNA modifications (i.e., 8-oxoG) in mRNA due to changes in the cell environment (i.e., oxidative stress) leads to a change in translation, leading to different phenotypic effects. Using mutational analysis and molecular dynamics simulations on the modification-specific protein readers (i.e., 8-oxoG reader PNPase), engineered species with increased affinity and selectivity for modified RNA can modulate the effects of environmental change (i.e., increased resistance to oxidative stress).

Figure 2.

(A) Schematic diagram of an electronic transistor. (B) Exemplified two-state (binary system) electrical output. (C) Example of truth tables for NOT, AND, and OR operations. (D) Exemplified view of the working principle light-up RNA aptamer acting as a switch ON and OFF. (E) Three-dimensional structures of some commonly used RNA light-up aptamers.

Figure 3.

Strategies for the delivery of RNA into cells. (A) Exosomes collected from cells are loaded with nucleic acid nanoparticles (NANPs) for their cellular delivery. (B) Chemically modified ribonucleic acid (cmRNA) encoding BMP-2 which is then complexed with polyethylenimine (PEI) enables polyplex formation and subsequent transfection.

Figure 4.

Current achievements, challenges, and biomedical opportunities for therapeutic nucleic acid nanoparticle (NANP) technologies. Achievements and opportunities are summarized along with barriers hindering NANPs’ translation from bench to clinic. IND, investigational new drug; IDE, investigational device exemption; GMP, good manufacturing practice; GLP, good laboratory practice; VLP, virus-like particle; APC, antigen-presenting cell.

Figure 5.

Schematic of the endosomal and cytosolic nucleic acid immune sensors that identify a targeted panel of triangular nucleic acid nanoparticles (NANPs) that differ in chemical composition but have the same connectivity, shape, size, charge, and sequence. NANPs are represented as triangles and the strands are color coded according to chemical composition (red = RNA, black = DNA, blue = 2′F-modified strands).