Engineered RNA Modification Recognition

Abstract Alida Biosciences Inc is developing a commercial platform for the analysis of the epitranscriptome, which is the totality of chemical modifications applied naturally to RNA to regulate possibly all aspects of RNA biology: transcription (mods are installed co-transcriptionally), translation, transcript lifetime, trafficking, alternative splicing, RNA folding, RNA–protein interactions, and more. The field of epitranscriptomics has seen rapid growth, motivated by the significance of this biology and the emerging opportunities to use RNA modifications as diagnostic biomarkers and to intervene in epitranscriptomic pathways as a promising novel paradigm in drug development, especially in cancer chemotherapy. Moreover, emerging evidence points to the significance of the epitranscriptome in optimizing RNA-based medicines. Alida’s platform technology will make epitranscriptomics accessible by offering a user-friendly workflow, integrated process controls, and cloud-based data handling and bioinformatics. In this SBIR grant, we seek to integrate our engineered RNA modification binding agents into our platform, develop and refine additional binders to expand the platform’s capabilities, and commercialize them in v2.0 of Alida Bio’s EpiPlex assay. The enhanced properties of the novel binding agents are optimized specifically for our platform to maximize sensitivity and selectivity, which is especially significant for high-value clinical samples in which only sub-nanogram quantities of RNA are likely to be available: needle biopsies, FFPE samples, and others. The high affinity and specificity of these binding agents will enable additional biotechnological applications beyond EpiPlex.