Current sequencing techniques are limited to short segments of DNA, requiring researchers to piece together the segments in a manner not unlike putting together a jigsaw puzzle. Yet researchers would like to examine sequences of whole sets of genes and other long segments of non-coding regions of the genome.
BioNano Genomics, a company located in San Diego, is making this possible through the use of nanoscale channel technology developed at Princeton. The company makes a genome mapping system called Irys®, which offers highresolution, single-molecule analysis of long strands of DNA. BioNano Genomics’ founder and chief scientific officer is Han Cao, who was a co-inventor of the technology while working as a postdoctoral researcher at Princeton.
The system takes advantage of nanoscale channels that are so narrow that they permit only one DNA molecule to travel through the channel at a time. At the entrance to the channel, micro- and nano-sized structures separate and uncoil the DNA strands and then direct them into the channel. While stretched and linearized inside the channel, fluorescently labeled DNA strands can be imaged by a detector that captures quantitative information about the features of the DNA molecule.
BioNano Genomics’ technology offers a large-scale view of the DNA molecule, letting researchers see where genes are located relative to each other. The technology also could potentially reveal other elements such as open reading frames, noncoding frames, repetitive regions and even epigenomic patterns. This information is often destroyed when DNA is cut up for use in traditional sequencers. The technology also can reveal sites of DNA damage, mutations and structural variations such as duplications, deletions, and extra copies of genes.
The technology was developed at Princeton by a multidisciplinary collaboration among faculty from the School of Engineering and Applied Science, the Department of Physics, and the Department of Molecular Biology. It was supported by a grant from the Defense Advanced Research Projects Agency. The inventors were: Cao; Steven Chou, the Joseph C. Elgin Professor of Engineering; Robert Austin, professor of physics; and former postdoctoral fellow Jonas Tegenfeldt.