Medicinal Genomics, a pioneer in the genomics of medicinal plants, today announced that the company has sequenced the entire genome of Cannabis sativa and Cannabis indica, assembling the largest known gene collection of this therapeutic plant. The DNA purification was performed at the company’s research facility in Amsterdam, and the sequencing was conducted by several service providers, including the latest long read technology from Roche’s 454 sequencing center.
Previously, only two million bases of Cannabis sequence have been deposited in GenBank, a sequence database provided by the National Center for Biotechnology Information (NCBI). To date, Medicinal Genomics has privately sequenced over 131 billion bases of sequence, which represents a 65,000 fold increase in what has been publicly shared about the Cannabis genome. Concurrently, Medicinal Genomics has published the raw reads from Cannabis sativa on Amazon’s EC2, a public cloud computing service, giving the scientific community access to conduct further research. The Cannabis indica genome sequence will be made available on the EC2 in a few weeks as well. The genome annotations will be made accessible via an iPad application that the company expects to launch in the fall.
“Despite compelling evidence of the therapeutic benefits of Cannabis, very little genomics research has been performed in this area,” said Kevin McKernan, founder and head of scientific operations of Medicinal Genomics. “Cannabis was one of the most difficult genomes that I ever sequenced, and even though only a draft assembly has been constructed, it is important to provide the scientific community with the raw data as quickly as possible. Ongoing scientific research suggests that some of the non-toxic compounds in this plant may ultimately prove to be powerful therapeutics that can treat a wide range of health conditions, including cancer and inflammatory diseases.”
More than 40 U.S. Food and Drug Administration (FDA) approved clinical trials evaluating Cannabis as a therapy have been completed or are underway, according to information obtained from www.clinicaltrials.gov.
“This is a significant accomplishment,” said Richard Gibbs, Ph.D., director of the human genome sequencing center at the Baylor College of Medicine. “It is excellent to see rapid data release policies being upheld by public and private organizations, particularly when it comes to such challenging genomes.”
With the complete genome in hand, researchers can begin to identify non-psychoactive compounds or enzyme pathways to better elucidate the therapeutic benefits of Cannabis, including the plant’s anti-cancer properties. These pathways can be optimized in the plant or cloned into other hosts for more efficient biologic production. In addition, it may be possible through genome directed breeding to attenuate the psychoactive effects of Cannabis, while enhancing the medicinal aspects.
Ongoing scientific research suggests that the Cannabis plant harbors beneficial compounds as it pertains to cancer apoptosis, antiemesis for HIV and chemotherapy patients, reduction of muscle spasms for multiple sclerosis patients, as well as the treatment of glaucoma, inflammatory diseases, anxiety, and post-traumatic stress disorder, among other health conditions. Of the 85 identified Cannabinoids in the plant, only one is independently psychoactive. The other 84 appear to be non-psychoactive and are still powerful therapeutics. Many Cannabinoids have been bred to low expression levels over the years but are excellent small molecule therapeutic drug candidates for cancer and inflammatory diseases. The genome sequence can be utilized to design breeding strategies to resurrect these nearly extinct pathways. In addition, Cannabinoids have also been shown to have a very favorable therapeutic index making them a unique class of anti-cancer compounds because the lethal dose is much higher than the effective dose. Furthermore, Cannabinoids are less addictive analgesics than opiates, and target different pain pathways in the body.
Another benefit of Cannabis as a source for a therapeutic drug is that its toxicity is low and well-known. This is unique in drug discovery where every drug candidate must go through expensive and lengthy clinical trials to establish its safety. With Cannabis, side effects have previously been established and might be mitigated with genome directed breeding, whereas many drug candidates are not easily modified and end up failing in clinical trials because of adverse effects on a small percentage of the population.
The American Medical Association, as well as the American College of Physicians each have independently issued reports on the medicinal benefits of Cannabis to justify a reclassification of the plant so it can be more easily researched. By digitizing the genome of Cannabis, researchers from around the world can now study this plant without having to handle it. Assembling the complete Cannabis genome was a logical first step to enable more comprehensive scientific research to begin.
Medicinal Genomics is the first known organization to sequence the complete genomes of Cannabis sativa and Cannabis indica. Aside from being a useful tool to discover small molecule therapeutic drug candidates, there are many other commercial applications of these sequences, including the design of genomic assays that measure genes predictive of Cannabinoid levels in the plants at seedling stages. Use of this information will enhance breeding strategies to develop high CBD or other medicinal traits into strains. These genomic assays can also be utilized to help regulate the medicinal Cannabis market through better oversight and labeling. The non psycho-active plant known as hemp is also a productive plant for fiber production and may benefit from genome sequencing in its pursuit to improve breeding programs.
The company was founded by Kevin McKernan, a recognized thought leader and innovator in DNA sequencing. Kevin co-invented a magnetic bead-based chemistry, called SPRI, which enabled fully automated nucleic acid purification for the Human Genome Project. Based on the SPRI technology, Kevin, along with his two brothers, founded Agencourt Bioscience, an efficient, low cost sequencing laboratory. Agencourt was the only commercial laboratory selected to participate in the Human, Rat, and Puffer Fish Genome Projects, in addition to serving as the lone sequencing facility for the Mammalian Gene Collection. Agencourt was sold to Beckman Coulter in 2005. Prior to the sale to Beckman, Agencourt spun off its subsidiary, Agencourt Personal Genomics, to its shareholders. Agencourt Personal Genomics was a next generation sequencing (NGS) project that Kevin had also co-invented, which subsequently became known as SOLiD. Agencourt Personal Genomics created an instrument that advanced the accuracy and throughput of NGS, lowering the cost of sequencing by a factor of 100,000. Nine months after the spin out, Agencourt Personal Genomics was purchased by Applied Biosystems, the then leader in DNA sequencers. Kevin remained with Applied Biosystems for 5 years, even after Applied Biosystems was acquired by Life Technologies, to complete the family of NGS products. He most recently served as vice president of advanced research and head of research and development for the Ion Torrent division of Life Technologies.
Medicinal Genomics maintains its corporate headquarters in Marblehead, Mass. All scientific operations are conducted at the company’s research facility in Amsterdam, Netherlands.