A long-held goal in sequencing has been to use a voltage-biased nanoscale pore in a membrane to measure the passage of a linear, single-stranded (ss) DNA or RNA molecule through that pore. With the development of enzyme-based methods that ratchet polynucleotides through the nanopore, nucleobase-by-nucleobase, measurements of changes in the current through the pore can now be decoded into a DNA sequence using an algorithm. In this Historical Perspective, we describe the key steps in nanopore strand-sequencing, from its earliest conceptualization more than 25 years ago to its recent commercialization and application.
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The authors are funded by the National Human Genome Research Institute of the National Institutes of Health award numbers HG006321, HG007827 and HG003703.
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All of the authors are members of the Technology Advisory Board of Oxford Nanopore Technologies, Oxford, UK, for which they receive compensation, including stock options of unknown value that may exceed $10,000. They are inventors on the following nanopore sequencing–related US patents owned by their respective universities: 5,795,782; 6,015,714; 6,267,193; 6,267,872; 6,362,002; 6,464,842; 6,428,959; 6,673,615; 6,746,594; 6,783,643; 6,936,433; 7,118,657; 7,189,503; 7,238,485; 7,258,838; 7,253,434; 7,466,069; 7,435,353; 7,468,271; 7,582,490; 7,803,607; 7,846,738; 7,993,538; 7,969,079; 8,092,697; 8,726,465.
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Deamer, D., Akeson, M. & Branton, D. Three decades of nanopore sequencing. Nat Biotechnol 34, 518–524 (2016). https://doi.org/10.1038/nbt.3423
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DOI: https://doi.org/10.1038/nbt.3423
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