RNA modifications, which constitute the epitranscriptome, play vital roles in seemingly all aspects of RNA metabolism and RNA's role in the Central Dogma. More than 170 naturally occurring chemical modifications to RNA are known, more than 60 of which are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA, andthe others. These modifications are dynamic; their global quantities change in development and during disease progression. They are installed by writer enzymes, read by reader proteins and removed by eraser enzymes,and they have an intrinsic capacity to alter RNA structure and dynamics. They influence translation initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and regulate RNA degradation. RNA reader, writer and eraser proteins are promising drug targets of high current interest to pharma. Despite this significance, no currently existing analytical method is capable of locating multiple RNA modifications simultaneously with precise locus information and stoichiometry. The focus of this application is to de-risk a positional marking approach to RNA modification analysis that is capable of multiplexing, approaching single base resolution. This technology will be significant because it will provide the first commercial method for profiling and correlating changes of multiple RNA modification types across the entire transcript me in a given sample.
Public Health Relevance Statement: Project Narrative Alida Biosciences is a start-up company focused on reading the epitranscriptomic code, a regulatory layer of biological information controlling how the genetic code is used in cells in health and in disease progression. By creating and commercializing the first methods for reading multiple elements of this epitranscriptomic code simultaneously, we will enable new science to understand the progression of diseases such as cancer and accelerate drug development targeting epitranscriptomic pathways.
Project Terms: Alternative Splicing, Alternate Splicing, Alternative RNA Splicing, Antibodies, Bar Codes, barcode, Biological Assay, Assay, Bioassay, Biologic Assays, Biological Sciences, Biologic Sciences, Bioscience, Life Sciences, Malignant Neoplasms, Cancers, Malignant Tumor, malignancy, neoplasm/cancer, Cells, Cell Body, Cytidine Deaminase, Cytidine Aminohydrolase, Cytosine, Deamination, Disease, Disorder, DNA, Deoxyribonucleic Acid, Drug resistance, drug resistant, resistance to Drug, resistant to Drug, Elements, Enzymes, Enzyme Gene, Exhibits, Foundations, Genetic Code, Goals, Health, Human, Modern Man, Methods, Peptides, Phenotype, Play, Proteins, Reading, Risk, Non-Polyadenylated RNA, RNA Gene Products, Ribonucleic Acid, RNA, mRNA, Messenger RNA, rRNA, Ribosomal RNA, Triplet Codon-Amino Acid Adaptor, tRNA, transfer Ribonucleic acids, Transfer RNA, social role, Role, Science, Technology, Genetic Transcription, Gene Transcription, RNA Expression, Transcription, Translating, Translations, Uracil, Virus Diseases, Viral Diseases, viral infection, virus infection, virus-induced disease, Work, Measures, Point Mutation, Chimeric Proteins, Chimera Protein, Fusion Protein, analytical method, base, tumor progression, cancer progression, neoplasm progression, neoplastic progression, Label, improved, Phase, Biological, biologic, Chemicals, Ligand Binding Protein, Ligand Binding Protein Gene, Protein Binding, bound protein, Binding Proteins, Disease Progression, Location, Best Practice Analysis, Benchmarking, interest, Deaminase, covalent bond, Performance, stoichiometry, RNA library, trafficking, Structure, Reporting, Position, Positioning Attribute, Coding System, Code, Sampling, drug development, Oranges, protein expression, RNA Degradation, APOBEC-1, APOBEC1, Apobec-1 protein, BEDP, CDAR1, HEPR, apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1, apoB mRNA editing catalytic subunit, Affinity, Reader, Resolution, Translation Initiation, Enzymatic Biochemistry, Enzymology, Preparation, Molecular, Process, Modification, Development, developmental, Pathway interactions, pathway, Coupling, commercialization, next generation sequencing, NGS Method, NGS system, next gen sequencing, nextgen sequencing, Drug Targeting, transcriptome, global gene expression, global transcription profile, experimental study, experiment, experimental research, mRNA sequencing, mRNA seq, mRNA-seq, mRNAseq, epitranscriptomics, epitranscriptome, RNA metabolism, base editing
