Programmable Nucleic Acid Based Polygons with Controlled Neuroimmunomodulatory Properties for Predictive QSAR Modeling. Issue 42 (18th September 2017) - Johnson, Morgan Brittany
Abstract: In the past few years, the study of therapeutic RNA nanotechnology has expanded tremendously to encompass a large group of interdisciplinary sciences. It is now evident that rationally designed programmable RNA nanostructures offer unique advantages in addressing contemporary therapeutic challenges such as distinguishing target cell types and ameliorating disease. However, to maximize the therapeutic benefit of these nanostructures, it is essential to understand the immunostimulatory aptitude of such tools and identify potential complications. This paper presents a set of 16 nanoparticle platforms that are highly configurable. These novel nucleic acid based polygonal platforms are programmed for controllable self‐assembly from RNA and/or DNA strands via canonical Watson–Crick interactions. It is demonstrated that the immunostimulatory properties of these particular designs can be tuned to elicit the desired immune response or lack thereof. To advance the current understanding of the nanoparticle properties that contribute to the observed immunomodulatory activity and establish corresponding designing principles, quantitative structure–activity relationship modeling is conducted. The results demonstrate that molecular weight, together with melting temperature and half‐life, strongly predicts the observed immunomodulatory activity. This framework provides the fundamental guidelines necessary for the development of a new library of nanoparticles with predictable immunomodulatory activity. Abstract : Nucleic acid nanoparticles are garnering wide attention for their advantages over traditional macromolecule and protein‐based pharmaceuticals; however, challenges remain in combating nanoparticles' unwanted immune responses. Here, the first predictive quantitative structure–activity relationship models are presented for discerning a given nucleic acid nanoparticle's immunomodulatory activity based on its measured physicochemical properties, size, and composition, which are experimentally shown to alter their immunogenicity.