Narrowing in on nanopore

SAN DIGEO—Illumina Inc. has licensed the rights to a DNA sequencing technology developed by professors from the University of Alabama at Birmingham (UAB) and the University of Washington (UW). No specific terms were released, but the license grants Illumina exclusive worldwide rights for the development and marketing of the nanopore DNA sequencing technology developed by Dr. Jens Gundlach, a physics professor at UW, and Dr. Michael Niederweis, a microbiology professor at the UAB School of medicine, and their teams. Patent pending applications co-owned by UW and the UAB Research Foundation cover the technology.

“Many companies and universities are looking at the potential of nanopore technology, but the technology developed by Drs. Niederweis and Gundlach is among the most promising,” Christian Henry, senior vice president and general manager of Illumina’s Genomics Solutions business, commented in a statement.

Nanopore sequencing has the potential to become a new standard in sequencing, providing a simpler, cheaper method. It consists of using a pore just large enough for a DNA strand to pass through, and as it does, it partially blocks an electrical current, which in turn lets each of the four DNA bases produce a unique electrical signal so the system can identify the sequence.

“Widespread access to genetic information will improve medical care worldwide, but in order to become part of daily, personalized medicine, DNA sequencing methods will need to become faster and cheaper,” said Niederweis in a press release. “Our nanopore technology promises to achieve that, and we believe Illumina can transform our experimental system into a pioneering commercial technology.”

The nanopore in question was created by genetically engineering a protein pore from a Mycobacterium smegmatis, resulting in a pore with an opening a mere one-billionth of a meter in size. Niederweis began studying these bacteria due to their unique composition: the outer membranes are capable of protecting mycobacteria from toxic compounds, including the antibiotics that destroy most bacteria. In 2004, Niederweis and colleagues published the structure of an M. smegmatis pore protein in Science, and four years later, Gundlach, Niederweis and their teams published an article in the Proceedings of the National Academy of Sciences demonstrating that given the shape of M. smegmatis’ pores, they are several times more sensitive for DNA sequencing than a previously used pore from Staphylococcus aureus.

An issue with DNA sequencing, however, was that the strands of DNA were moving through nanopores too quickly for their electric signatures to register, a problem Niederweis, Gundlach and their teams solved by introducing DNA polymerase, which paces DNA strands, reading their genetic code before genetic instructions are carried out. In this sequencing system, the polymerase attaches itself to DNA strands heading for the pore, but since it is too big to fit through the opening, the DNA strands pass through the pore as the polymerase processes them—one nucleotide at a time—resulting in speeds that can be easily detected electronically. The teams published another study in 2012 in Nature Biotechnology that detailed how the combination of a genetically altered M. smegmatis pore and DNA polymerase can be used to determine DNA sequences using single DNA molecules.

Gundlach noted in a press release that this technique can be used to identify epigenetic modifications in DNA, “subtle DNA modifications that happen over the lifetime of an individual.”

“Epigenetic modifications are important for things like cancer,” Gundlach added, “and being able to provide DNA sequencing that can directly identify epigenetic changes is one of the charms of the nanopore sequencing method.”