US Genomics is developing technology to do linear single strand DNA analysis. They are not the only ones attempting this and it is not clear how successful they will be. But they have made progress jumping over some of the hurdles that they face with their approach. Notice the high speed per minute. At that rate they could in theory read the entire 3 billion DNA sequence of a human genome in less than 11 days..
Chan has developed a way to spool out the tangle of DNA in a chromosome using a 'nanofluidic' chip smaller than a computer key. Fluid flowing through the chip draws the DNA through an array of pegs like bowling pins. One end works loose and is drawn into a funnel at the end.
Rather than sequencing every letter, Chan and his team spot the differences between individuals — and use the reference genome to fill in the rest. Fluorescent tags stick to variable spots; a detector reads their order as they flow past. The speed-reading technique gets through around 200,000 letters a minute, he claims.
They are trying to develop the ability to unravel and read thru a genome as fast as a regular cell can when it replicates its genome during cell division.
The company's technologies are premised upon the direct and linear reading of large sections of genomes. Linear analysis is powerful because there is no upper limit on the size of DNA that is read. Furthermore, this is the method which nature has perfected over millions of years. DNA, during cell division, is replicated with DNA polymerase, an enzyme that tracks along DNA in a linear fashion. Identification of the bases is mediated by base-pairing and enzyme-DNA specific interactions. By reproducing nature's method of DNA reading, the highest readout speeds are possible. A human cell can replicate and read its DNA in less than thirty minutes. The company's technology is a biophysical rendering of the polymerase-DNA interaction and allows for speeds on the same time scale as nature's DNA polymerases.
U.S. Genomics's technology platform, the GeneEngine™, has two components, (1) nanotechnology systems for positioning DNA so that it can be read linearly (broadly termed DNA Delivery Mechanism(s)™) and (2) detection technologies that allow the reading of information from the DNA Delivery Mechanism(s)™. The combination of different DNA Delivery Mechanism(s)™ with particular technologies makes possible different applications in genomic analysis, such as complete genome analysis, sequencing, polymorphism analysis, and gene expression determination.
Here's the announcement for their patent for moving single DNA strands past a reader sensor.
US Genomics is getting US military money to develop their technology to detect bioweapons attacks:
Woburn, MA (JUNE 13 2001) – U.S. Genomics announced today that its first patent has been granted by the United States Patent and Trademark Office (6,210,896 Molecular Motors). The issued patent covers the first of a suite of proprietary techniques that U.S. Genomics has developed to allow the direct, linear reading of extremely long sequences of DNA.
Specifically, the patent covers the Company's technology for using molecules that interact with cellular polymers (such as nucleic acid -- DNA or RNA) in such a way that the molecules cause the polymers to move. The segments of the polymer that are moved by the "molecular motor" flow past a fixed point, emitting specific signals that reveal genetic information embedded on the strand of nucleic acid.Eugene Chan, Chairman and CEO of U.S. Genomics, commented, "The granting of this first patent for U.S. Genomics is a validation of our approach to direct linear analysis of DNA. Modeled after the nearly instantaneous readings of DNA that natural cellular machinery executes, our approach to deciphering and understanding genetic information is directed towards complete-genome analysis - reading the entire sequence of genetic coding contained in a full, unbroken strand of DNA." U.S. Genomics has developed the GeneEngine™, a set of laboratory devices that enable researchers to uncurl and separate individual strands of DNA or RNA which are then run through a microarray sequencer in extremely long, unbroken, linear segments. The genetic information captured through such direct linear readings is relatively much more comprehensive and integrated than data available through other current techniques. The molecular motors covered in this first patent provide the physical mechanism for moving the strands of DNA through the sequencer.
Woburn, MA (September 04, 2002) – U.S. Genomics announced today it was awarded a $499,500 contract by the Defense Advanced Research Projects Agency (DARPA) to examine the use of the Company’s direct linear DNA analysis technology to detect Class A pathogens, such as anthrax and smallpox. The contract will enable the company to study the use of its GeneEngine™ technology as a tool to create genomic maps or signatures of organisms; such maps have the potential to enable very rapid detection and identification of deadly bacteria.
While they do not sound like they are going to be ready to ship fully working products any time soon they have entered into an agreement The Wellcome Trust Sanger Institute to try out their GeneEngine technology in the study of genetic variations.
It is hard to interpret the announcement with The Wellcome Trust Sanger Institute. When will US Genomics deliver usable technology and what will that initial technology be capable of?
Woburn, MA (January 28, 2002) – U.S. Genomics and The Wellcome Trust Sanger Institute have entered into a collaboration to examine the use of U.S. Genomics’ direct, linear DNA analysis technology in research on the human genome. The partnership will study the use of this new technology to investigate human genetic data at a level of complexity, comprehensiveness, and accuracy not previously studied. The collaboration marks the first application of U.S. Genomics’ technology in an outside research setting.
Under the agreement, The Wellcome Trust Sanger Institute and U.S. Genomics will jointly employ their scientific expertise to conduct genetic research using the GeneEngine™ technology and other aspects of U.S.Genomics’ technology platform. The research collaboration will explore the application of U.S. Genomics’ technology to human genetic analysis at the highest level of detail and complexity. Financial terms of the agreement were not disclosed.
If we step back and look at it from a higher level what is interesting about this company and others like it is that venture capitalists are funding attempts to drive down the cost and accelerate the speed of DNA sequencing by orders of magnitude. Some of these companies will succeed. A lot of progress has already been made.
The US Genomics press releases are here.
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