During this program, Electronic BioSciences (EBS) along with our associated team of field experts, aim to solve the technical challenges associated with the development of a completely new and enabling nanopore- based sequencing platform along with the associated methodology for sequencing DNA at the single nucleotide level, with the capability to directly correctly identifying chemically modified nucleotides. During this project, we will specifically be focused on 5-methylcytosine (5mC) and N6-methyladenine (m6A), before pursuing variants and other modifications. At present, the scientific community?s understanding of the ?epigenome,? i.e. the chemical modifications which regulate the function of DNA, is still in its infancy. While there are many known chemical modifications to either the base or sugar-phosphate backbone of nucleic acids, due to the lack of analytical characterization methods available, the exact roles of these modifications remain to be determined. New technologies capable of elucidating the role of these modifications have the potential to revolutionize the use of the epigenome. At the conclusion of this Phase 1 project, we will have successfully overcome the known limitations with exonuclease-based sequencing concepts, that being capture efficiency and nucleotide identification, which will represent a significant scientific breakthrough.
There is a current need within the field of next generation sequencing (NGS) for new, enabling instrumentation, capable of high accuracy, direct, native DNA sequencing, including the identification of canonical and modified bases and the correct characterization of homopolymer stretches and repeating sequences. The direct sequencing of chemical modifications in the genome with high accuracy would facilitate an explosion of epigenetic sequencing data. These results would better enable the use of these markers in clinical diagnostics and prognostics, provide a deeper understanding of infectious diseases, allow cultivation of better crops, and advance our basic understanding of all domains of biology, in addition to empowering unforeseen fields, such as epigenomic diagnostics and therapeutics; thus, the methodology/technology that will be developed during this project has the potential to revolutionize the use of the genome and epigenome, radically changing standard practices as well as enabling diagnostics and therapeutics.
