SBIR-STTR Award

More than 170 naturally occurring chemical modifications to RNA are known, more than 100 of which are foundin human RNA of all types: mRNA, tRNA, rRNA, lncRNA, and the others. These modifications play a central rolein nearly all aspects of RNA function, such as translation initiation and termination, translation fidelity, alternativesplicing, trafficking between cellular compartments, and regulating RNA degradation. Proteins that install, read,and remove modifications are promising drug targets of high current interest to pharma. Currently availableanalytical methods either do not report on sequence context or provide sequence information but at the expenseof multiplexing capability. Despite these limitations, it is now known that modifications are dynamically tied tophenotypic changes in cancer progression, drug resistance, and viral infection. The focus of this application isto de-risk a new approach to RNA modification analysis capable of reading any set of RNA modifications in amultiplexed reaction, approaching single base resolution. This technology will be significant because it willprovide the first method for profiling and correlating changes of multiple RNA modification types across the entiretranscriptome 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 ; Antibody Affinity ; antigen antibody affinity ; Architecture ; Engineering / Architecture ; Bar Codes ; barcode ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biological Sciences ; Biologic Sciences ; Bioscience ; Life Sciences ; Complementary DNA ; cDNA ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cells ; Cell Body ; Chemistry ; Disease ; Disorder ; DNA ; Deoxyribonucleic Acid ; Drug resistance ; drug resistant ; resistance to Drug ; resistant to Drug ; Elements ; Exhibits ; Face ; faces ; facial ; Foundations ; Gene Expression Regulation ; Gene Action Regulation ; Gene Regulation ; Gene Regulation Process ; Genetic Code ; Health ; Human ; Modern Man ; Immunoprecipitation ; Immune Precipitation ; Libraries ; Ligation ; Closure by Ligation ; Methods ; Oligonucleotides ; Oligo ; oligos ; Phenotype ; Play ; Proteins ; Reading ; Research Personnel ; Investigators ; Researchers ; Risk ; RNA ; Non-Polyadenylated RNA ; RNA Gene Products ; Ribonucleic Acid ; Messenger RNA ; mRNA ; Ribosomal RNA ; rRNA ; Transfer RNA ; Triplet Codon-Amino Acid Adaptor ; tRNA ; transfer Ribonucleic acids ; Role ; social role ; Science ; Technology ; Testing ; Genetic Transcription ; Gene Transcription ; RNA Expression ; Transcription ; Translations ; Virus Diseases ; Viral Diseases ; viral infection ; virus infection ; virus-induced disease ; Work ; Measures ; Site-Directed Mutagenesis ; Site-Specific Mutagenesis ; Targeted DNA Modification ; Targeted Modification ; analytical method ; base ; density ; tumor progression ; cancer progression ; neoplasm progression ; neoplastic progression ; Label ; Surface ; Phase ; Variant ; Variation ; Biological ; Medical ; Chemicals ; Individual ; Disease Progression ; Diagnostic ; Dimensions ; Complex ; Reaction ; Location ; interest ; experience ; stoichiometry ; antibody conjugate ; trafficking ; Reporting ; Position ; Positioning Attribute ; Coding System ; Code ; Sampling ; drug development ; Primer Extension ; Resolution ; Translation Initiation ; Enzymatic Biochemistry ; Enzymology ; Preparation ; Molecular ; Modification ; Development ; developmental ; Pathway interactions ; pathway ; design ; designing ; novel strategies ; new approaches ; novel approaches ; novel strategy ; nanopore ; nano pore ; innovation ; innovate ; innovative ; commercialization ; next generation sequencing ; NGS Method ; NGS system ; next gen sequencing ; nextgen sequencing ; Drug Targeting ; personalized medicine ; personalization of treatment ; personalized therapy ; personalized treatment ; RNA immunoprecipitation sequencing ; RIP seq ; RIPseq ; transcriptome ; global gene expression ; global transcription profile ; experimental study ; experiment ; experimental research ; mRNA sequencing ; mRNA seq ; mRNA-seq ; mRNAseq ; epitranscriptomics ; epitranscriptome ;

Epitranscriptomics is the study of RNA modifications, which include more than 170 naturally occurring chemicalalternations to the nucleotides. More than 60 are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA,and the others. These modifications are dynamic; their global quantities change in development and duringdisease progression. They are installed by writer enzymes, read by reader proteins and removed by eraserenzymes, and they have an intrinsic capacity to alter RNA structure and dynamics. They influence translationinitiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, andregulate RNA degradation. RNA reader, writer and eraser proteins are promising drug targets of high currentinterest to pharma. Currently available analytical methods either do not report on sequence context or providesequence information but at the expense of multiplexing capability. Despite these limitations, it is now knownthat modifications are dynamically tied to phenotypic changes in cancer progression, drug resistance, aging, andviral infection. Alida Biosciences is developing a new commercial platform to detecting, identifying, and mappingRNA modifications in a multiplex and with high sensitivity-suitable for clinical samples (e.g. needle biopsies,FFPE samples) in which low quantities of RNA may be available. Following completion of our Phase I milestonesfocused on creating the new multiplexed assay and proof-of-concept testing, this proposal aims to (1) completeassay development, optimizing sensitivity, specificity, and a robust and user-friendly workflow, (2) develop assayautomation, and (3) perform assay validation in preparation for commercial launch. This technology will besignificant because it will provide the first commercial platform capable of profiling and correlating changes ofmultiple RNA modification types across the entire transcriptome 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 platform 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: