An important new gene discovery technology developed at Cold Spring Harbor Laboratory has been licensed to Orion Genomics, LLC of St. Louis, MO. The technology, known as methyl filtration, is a method for rapid and economical sequencing of large, complex genomes. The methyl filtration technology is described in the November 1, 1999, issue of the British scientific journal, Nature Genetics. 

Under the terms of the agreement announced today, Orion Genomics has obtained exclusive, world-wide commercial rights to the technology for all fields of use. 

Dr. James D. Watson, Nobel Laureate and President of Cold Spring Harbor Laboratory said: “This new technology has significant potential to accelerate the understanding of economically important plant species. We chose Orion Genomics as our exclusive commercial licensee because we believe that they bring together the expertise to implement complex genomic technologies to realize this potential.” 

The new technology, to be commercialized under the GeneThresherTM brand name, will allow scientists at Orion Genomics, on behalf of its research and business partners, to directly sequence and find the genes of economically important plant species many times faster and at much reduced cost compared to even the best currently available technologies. Experiments at Cold Spring Harbor Laboratory and at Orion Genomics have shown that the GeneThresherTM technology can reduce the time and cost of sequencing required to find genes by 5- to 20-fold depending on the species involved.

“The GeneThresherTM technology will have a significant impact on the rate of gene discovery in all plant species” said Dr. Richard K. Wilson, CEO of Orion. “We are very excited to have exclusive commercial rights to this breakthrough technology, which complements our capabilities in structural genomics.” 

Background: 

The genomes of many complex organisms, particularly the major agricultural crop species, represent enormous opportunities for product discovery. But many of these important genomes have been out of reach of even the largest product discovery programs due to the enormous costs involved in “whole genome” sequencing. The major reason whole genome sequencing approaches in large, complex genomes are so prohibitively expensive is that the genomes of higher plants and animals are made up of a relatively small proportion of genes scattered among a large proportion of repetitive, intergenic, non-coding (or “junk”) DNA.

The EST (expressed sequence tag) sequencing approach used by many companies avoids this intergenic and non-coding DNA, but suffers from other limitations. Many potentially important genes are under-represented or absent in the cDNA libraries used in EST approaches. Data from human, mouse, nematode and Arabidopsis EST efforts suggest that between 30 and 50 percent of genes are missed even at very high sequence coverage. 

Recently, researchers at Cold Spring Harbor Laboratory (CSHL) and others showed that the bulk of the repetitive, intergenic, non-coding DNA in plants is methylated, and therefore distinguishable from genes. Dr. Robert A. Martienssen Dr. W. Richard McCombie and Dr. Pablo Rabinowicz, (the scientists at CSHL who invented the newly-licensed technology), have demonstrated in maize that much of this methylated, non-coding DNA can be eliminated by “filter cloning” genomic libraries in a series of engineered bacterial strains. The data show that the methylated DNA is eliminated and the unmethylated, genic regions containing known genes are preserved in these filtered libraries. Most importantly, the data show that unique sequences not found in EST databases are richly represented in the filtered libraries. Therefore, the use of the CSHL  technology to filter large genomes greatly reduces the number of sequencing reactions required to find most of the genes. The new technology will also find many genes that may not be found with EST approaches. 

Orion Genomics LLC was founded in 1998 by a group of academic scientists working on the Human Genome Project. They are Dr. Richard K. Wilson and Dr. John D. McPherson, faculty members at Genome Sequencing Center at Washington University School of Medicine in St. Louis, Missouri, and Drs. Martienssen and McCombie from CSHL. Orion Genomics engages in the discovery and development of gene-based agricultural products, in collaboration with agricultural companies and in its own proprietary programs. The Company will market its products through its collaborations and through out-license arrangements. 

Cold Spring Harbor Laboratories is recognized internationally for its excellence in basic research (including plant biology, cancer and neurobiology) as well as a wide range of educational activities that include extensive postgraduate courses and a Ph.D. program in the Watson School of Biological Sciences. The Laboratory also hosts numerous scientific meetings each year attended by more than 6,500 biologists from around the world.  The laboratory is headed by Director Bruce Stillman and President James D. Watson.

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