Oxford Nanopore, formerly UK’s Oxford NanoLabs, has licensed nanopore technology from Harvard to help advance the company’s sequencing methods for DNAs and other molecules. This is not the first time we are reporting about the efforts to commercialize nanopore channels as DNA sequencing sites, since scientists have known for a while now about the ability of these channels to interact with translocating molecules, and “report” their molecular structure. (Check out the flashbacks below for previous posts on nanopore-assisted single molecule sequencing research.)
From the press release by Oxford Nanopore:
Under the terms of this agreement with Harvard, Oxford Nanopore has exclusive rights to develop and commercialise a number of nanopore technological breakthroughs developed in the laboratories of three investigators at Harvard and their collaborators at the University of California Santa Cruz (UCSC) and the National Institute of Standards and Technology (NIST), an agency of the US Department of Commerce. The investigators include: Professors Daniel Branton, George Church and Jene Golovchenko at Harvard; David Deamer and Mark Akeson at UCSC and John Kasianowicz at NIST.
These academics have pioneered the research of DNA translocation through nanopores and the potential for DNA sequencing using this method. This is complementary to the work of Professor Hagan Bayley, the founder of Oxford Nanopore Technologies. Professor Bayley pioneered the field of nanopores as sensors of single molecules, with a specific focus on the identification of DNA bases.
From the company’s technology page:
The nanopore sequencing method under development at Oxford Nanopore Technologies, BASE™ technology, is label-free and measures single DNA bases directly. The method does not rely on amplification or labelling, and provides a direct electrical signal for base calling. Whilst the evolution of other technologies relies on improvements in existing chemical, optical or bioinformatics procedures, nanopores would bypass these to deliver a genuinely revolutionary sequencing method.
The natural α-hemolysin nanopore alone is not capable of DNA sequencing. Oxford Nanopore is using protein engineering techniques to adapt the nanopore for the detection of DNA bases.
A key achievement in adapting the nanopore has been the covalent attachment of a cyclodextrin molecule to the inside surface of the nanopore, This acts as a binding site for individual DNA bases and allows accurate measurement of their passage through the nanopore binding site.
Furthermore, Oxford Nanopore is addressing the issue of how DNA is passed through the nanopore by adopting a novel exonuclease sequencing approach. This takes advantage of the ability of exonuclease enzymes to process DNA and cleave individual bases from the end of a DNA strand. By positioning an exonuclease in the correct position on a nanopore, the enzyme can potentially deliver individual DNA bases in sequence into the nanopore for rapid and accurate identification.
The natural α-hemolysin nanopore alone is not capable of DNA sequencing. Oxford Nanopore is using protein engineering techniques to adapt the nanopore for the detection of DNA bases.Technology page: Nanopores and BASE™ technology…
Press release: Oxford Nanopore and Harvard University agreement…
Flashbacks: Nanopore-based Single-Molecule Spectroscopy; Using Nanopore Channels to Sort DNA; Nanopore Method for DNA Sequencing
Upper side image: Alpha-hemolysin mutant to facilitate a molecular adapter for improved analyte detection and discrimination. This nanopore is shown with a custom cyclodextrin providing the binding site.