The Biotech Industry's Desire to Commercialize CRISPR-Cas9
By Zach Schultz
To solve complex diseases, researchers turned to simple organisms for inspiration.
MAMMALS ARE NOT the only living organisms that must deal with viruses. While mammals have complex immune systems to protect from viral infections, bacteria, which are also at risk of being infected by viruses, address the threat in a different manner. To understand how bacteria protect themselves from viral infections, it's important to understand what viruses do once they are inside an organism.
You may have heard that viruses are typically considered to be non-living; this is because viruses are unable to reproduce on their own. Once a virus breaks through a cell's wall, it inserts its genetic material into the host cell. This genetic material is then inserted into the host cell's DNA, and when the host cell uses its DNA to create proteins, it creates proteins encoded by the virus's DNA, as well.
This results in the cell creating more components of the virus. Once the new viruses form within the cell, they escape the cell and go on to infect another cell, continuing to reproduce by hijacking the host cell.
Bacteria defend against viruses by utilizing the virus's tendency to insert its genetic material into the bacteria's DNA. When bacteria recognize foreign genetic material within the cell that has yet to insert itself into the bacterial DNA, the bacteria take sequences of the foreign genetic material and insert them into a specific place in its own DNA known as a clustered regularly interspaced short palindromic repeat locus, or CRISPR locus.
The bacteria also contain various proteins known as CRISPR-associated proteins or CAS proteins for short. When the bacteria transcribes the DNA present in the CRISPR locus, it creates a guide RNA or gRNA for short. This gRNA binds to a specific Cas protein, known as Cas9. The molecule created by the gRNA and Cas9 protein then moves along the bacteria's DNA, looking for sections of the DNA that match up with the sequence of bases present in the gRNA.
Since the gRNA was created from a virus's genetic material, a match between the gRNA and a sequence of DNA in bacteria means that a virus had infected the bacteria and inserted its genetic material. In order to prevent the bacteria from creating more viruses when the bacteria transcribes its DNA into various proteins, the Cas9 protein cuts out the portion of DNA belonging to the virus, preventing the bacteria from making more copies of the virus.
Since the Cas9 protein can cut out unwanted sections of DNA, scientists began to wonder: can this be used not only to edit genomes selectively but also as a potential cure for genetic disorders?
As researchers continue to improve upon the implementation of CRISPR-Cas9 in therapeutic capacities, there is hope to correct diseases that were once thought to be incurable. Take, for example, Cystic Fibrosis. Cystic Fibrosis is an autosomal recessive disease, meaning that two copies of a defective CF gene, one from the mother and one from the father, were inherited by the child.
With two defective copies of the CF gene, the child is unable to make a functional protein that is used to regulate the movement of salt in and out of cells. This commonly results in difficulty breathing and digestive problems. Due to the genetic nature of this disease, the Cystic Fibrosis Foundation is hoping that CRISPR-Cas9 may provide a solution, and is already funding drug development to find out.
In 2016, Cystic Fibrosis Foundation Therapeutics pledged up to $5 million to Editas Medicine, a company founded by two scientists, Feng Zhang and George Church, who helped develop CRISPR-Cas9 for use in humans. Although treatment is still in the early stages of development, researchers have demonstrated that CRISPR-Cas9 was able to correct the mutation present in the CF gene in intestinal stem cells.
The business aspect of CRISPR-Cas9 simmers down to a patent battle between the University of California, Berkeley alongside the University of Vienna, and the Broad Institute of MIT and Harvard. In the University of California, Berkeley's and University of Vienna's corner: Jennifer Doudna and Emmanuelle Charpentier, the co-discoverers of the technology and owners of the original patent for the use of CRISPR-Cas9. In the Broad Institute's Corner: Feng Zhang and George Church, who patented the use of CRISPR-Cas9 in humans.
Within the United States, the Broad Institute is currently winning the patent battle for the use of CRISPR in humans, but in July of 2017, The University of California, Berkeley appealed the decision made by the United States Patent Trial and Appeal Board (PTAB), claiming the PTAB wrongly sided with the Broad Institute when it ruled the Broad Institute invented the use of CRISPR-Cas9 in eukaryotic cells, or cells that have a nucleus and membrane-bound organelles. In China, Europe, and the United Kingdom, though Doudna and Charpentier hold the patents for CRISPR-Cas9.
Both groups are eager to win the global patent battles, and the scientists have all ventured into the business world to capitalize on the technology. Jennifer Doudna is a founder of Caribou Biosciences and Intellia Therapeutics. Caribou is utilizing CRISPR-Cas9 for advancements in therapeutics, agriculture, biological research, and industrial biotechnology. Intellia Therapeutics focuses on the therapeutic potential of CRISPR-Cas9, looking to address severe illnesses that may be cured with this technology.
Intellia Therapeutics went public May of 2016, generating $108 million for the company. Emmanuelle Charpentier is a founder of CRISPR Therapeutics, which collaborates with Vertex Pharmaceuticals for research, and has established a joint venture with Bayer AG to advance CRISPR-Cas9 technology for use in humans and nonhumans. CRISPR Therapeutics' October 2016 IPO generated $56 million. Zhang Feng and George Church are founders of Editas Medicine, which focuses on the development of genome editing to cure disease. Editas was the first CRISPR biotech company to go public, and in its February 2016 IPO, Editas generated $94 million.
The success of the companies largely depends on the legal battles over the patents which the biotech companies have licenses to use. Beyond the patents, though, the companies are also evaluated on their ability to create a product through the research being conducted, which is funded by investors who are eager to see results. The biotech companies must also be cognizant of the continual scientific advances being made in the field of gene editing.
The companies with the correct patent licenses, ability to create a product from its research, and capacity to make advances in the field of gene editing will rise to the top, assuming the financial aspects of their companies remain sound. At this point in time though, it would be too early to predict the plights of the companies within the genome editing market.
Photo by Chuttersnap