Phase I Amount
$1,000,000
During this program, Electronic BioSciences (EBS) will fully develop and demonstrate a completely new RNA sequencing technology capable of directly sequencing the most common product of RNA editing: inosine (I). Cells diversify the coding potential of their mRNA and regulatory small RNAs by enzymatic conversion of adenosine (A) to I, i.e., A-to-I editing, in which the edited base codes differently in mRNA, guides alternative mRNA splicing, and renders miRNA and tRNA functional in cells. The current inability to directly sequence sites of A-to-I RNA editing with quantitative readout (i.e., profile or determine their ratio within given sequences) seriously limits the ability of researchers to fully understand this epitranscriptomic process in disease. Thus, EBS aims to fill this technology gap by developing a single-molecule sequencing technique capable of directly identifying the four canonical nucleotides along with I, all with high resolution and high accuracy. In turn, such a technology development will improve the understanding of RNA function, including the role and significance of I, to enable better diagnostics, prognostics, and therapeutics. At the end of this Phase II effort, EBS will have developed a beta-prototype I sequencing system and demonstrated its complete functionality and analytical capabilities for a variety of RNA types as well as benchmarked the sequencing results against current state-of-the-art approaches.
Public Health Relevance Statement: Project Narrative The technology that will be developed during this project, which can accurately call A-to-I editing sites, will be harnessed for early disease and illness detection, to provide information to decipher molecular mechanisms involved in disease initiation and progression, to monitor therapeutic outcomes and the impact on progression of the disease, and to monitor the success of novel treatments. Thus, the system we are proposing to develop, capable of directly detecting, differentiating, and sequencing A-to-I editing sites, has the potential to identify and analyze the epitranscriptomic signatures associated with viral infections, neurological disorders, Alzheimer's disease, as well as a broad spectrum of cancer types to enable better diagnostics, prognostics, and therapeutic interventions.
Project Terms: Achievement; Achievement Attainment; Adenosine; Algorithms; Alzheimer's Disease; AD dementia; Alzheimer; Alzheimer Type Dementia; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimer's disease dementia; Alzheimers Dementia; Alzheimers disease; Primary Senile Degenerative Dementia; dementia of the Alzheimer type; primary degenerative dementia; senile dementia of the Alzheimer type; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cause of Death; Cell Culture Techniques; cell culture; cell cultures; Cells; Cell Body; Communities; Disease; Disorder; Enzymes; Enzyme Gene; Exonuclease; Foundations; Goals; Guanosine; Hemolysin; Hemalysins; Human; Modern Man; Inosine; Libraries; Methods; Persons; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; nervous system disorder; Nucleotides; Reading; Research; Investigators; Researchers; Research Personnel; Risk; Non-Polyadenylated RNA; RNA Gene Products; Ribonucleic Acid; RNA; Splicing; RNA Splicing; mRNA; Messenger RNA; Triplet Codon-Amino Acid Adaptor; tRNA; transfer Ribonucleic acids; Transfer RNA; social role; Role; Societies; Software; Computer software; Technology; Temperature; Testing; Time; United States; Virus Diseases; Viral Diseases; viral infection; virus infection; virus-induced disease; Viscosity; Work; RNA Editing; RNA, Messenger, Editing; base; sensor; improved; Procedures; Site; Phase; prognostic; Individual; Disease Progression; Therapeutic; tool; instrument; Diagnostic; programs; Techniques; System; Amentia; Dementia; Best Practice Analysis; Benchmarking; mutant; success; tech development; technology development; novel; Coding System; Code; intervention therapy; Therapeutic Intervention; Modeling; Sampling; Property; single molecule; MicroRNAs; Micro RNA; miRNA; miRNAs; nerve stem cell; Neural Stem Cell; neural precursor; neural precursor cell; neural progenitor; neural progenitor cells; neuron progenitors; neuronal progenitor; neuronal progenitor cells; neuronal stem cells; neuroprogenitor; Small RNA; Age-Years; Detection; Reader; Resolution; therapy outcome; therapeutic outcome; Monitor; Preparation; Molecular; Process; Modification; Therapeutic Effect; Development; developmental; age related; age dependent; nanofabrication; nano fabricate; nano fabrication; nanofabricate; nanoscale; nano meter scale; nano meter sized; nano scale; nanometer scale; nanometer sized; nanopore; nano pore; cancer type; data acquisition; prototype; high risk; high reward; transcriptome sequencing; RNA Seq; RNA sequencing; RNAseq; sequencing platform; epitranscriptomics; RNA-targeting therapy; RNA targeting drug; RNA targeting therapeutics; base editing
