Engineered RNA Modification Recognition

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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. Alida’s platform technology will make epitranscriptomics more accessible by offering a user-friendly workflow, integrated process controls, and cloud-based data handling and bioinformatics. In this SBIR grant, we seek to develop engineered RNA modification binding agents for integration into our platform. The enhanced properties of the novel agents will be 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.