Caribou Biosciences was formed in 2011 to use CRISPR (Clustered Regularly Interspaced Palindromic Repeats) technology, based on a bacterial defense system against viruses, as a biotechnology tool. Co-founder and CEO Racheal Haurwitz was formerly a PhD student mentored by co-founder Jennifer Doudna at UC Berkeley, one of the inventors that turned this bacterial defense system into a customizable gene editing system.
Caribou Biosciences is applying CRISPR-Cas technology to therapeutics, agriculture, biological research and industrial biotech. Caribou co-founded Intellia Therapeutics in 2014 to use CRISPR-Cas9 to develop cures to diseases like blood disorders and cancer. Caribou is also working on developing medicine for pets and agricultural livestock. It is working on antimicrobial therapies and the large-scale production of biological therapeutics. In a TechCrunch interview Haurwitz said that Caribou Biosciences has no plans to edit human embryos.
CRISPR sequences contain copies of viral DNA sequences that the bacteria use as a guide to locate invading viral DNA. The CRISPR system makes an RNA guide for the target sequence that directs a Cas (CRISPR-associated) protein to cut foreign DNA. Dr. Jennifer Doudna at UC Berkeley and Dr. Emmanuelle Charpentier now at Max Planck Institute for Infection Biology, Berlin, co-invented the CRISPR-Cas9 gene editing system, which makes it possible for scientists to design custom RNA guides that target CRISPR-Cas9 to a desired genetic sequence in any genome for editing.
When CRISPR induces double stranded DNA breaks the cellular repair process causes some of the DNA sequence to be lost, which can disrupt gene function. While targeted disruption of genes is useful for some applications, the ability to change the DNA sequence to that of an introduced DNA template has broadened the applications of this technology. It is also possible to use CRISPR-Cas to make certain DNA changes without cutting. A modified CRISPR system uses a form of Cas9 with its cutting function inactivated, combined with other proteins to turn up or down gene expression levels without changing the DNA sequence.
There is a patent dispute between Doudna’s research team and the Broad Institute (MIT and Harvard) over the invention of CRISPR-Cas9 technology for use in human cells. The US patent granted to the Broad Institute is under appeal. The European patent office has revoked this first patent obtained by the Broad Institute citing lack of novelty. The European patent office has granted patents to the University of California and University of Vienna. One for using the CRISPR-Cas9 system across prokaryotic and eukaryotic systems and another for a modified form of CRISPR-Cas9 to regulate gene expression. Numerous patents have been assigned to Caribou Biosciences for CRISPR-Cas9 adaptations and other molecular biology materials.
Caribou Biosciences co-founded Intellia Therapeutics to use the Caribou CRISPR-Cas9 platform to develop therapeutics. Intellia Therapeutics is working with Regeneron to develop a gene knockout strategy for Transthyretin Amyloidosis (ATTR). CRISPR-Cas9 technology to knock out Hepatitis B Virus is being tested in animal models. Intellia is also developing the technology for gene editing in Alpha-1 Antitrypsin Deficiency (AATD) and Primary Hyperoxaluria (PH-1). Novartis is collaborating with Intellia to edit hemopoietic stem cells ex vivo at the BCL11A gene to treat Sickle Cell Disease. The two companies are also collaborating on Chimeric Antigen Receptor T Cell (CAR-T) strategies which modify the immune system so it better targets cancer.
Caribou Biosciences is developing cancer treatments in-house that target microbes that live on humans and other anti-microbial therapies.
Caribou Biosciences is collaborating with animal genetics company Genus (Basingstoke, UK) to improve the welfare of food producing animals. They are developing Porcine Reproductive and Respiratory Syndrome virus (PRRSv) resistant pigs. CRISPR-Cas9 technology was used to edit the CD163 gene in pigs, which makes the PRRSv unable to infect them.
DuPont collaborated with Caribou Biosciences to create drought and disease resistant waxy corn with CRISPR gene editing.
The Caribou technology platform is used to investigate the role of gene mutations in disease and find druggable targets. Manipulating gene function with CRISPR-Cas9 technology is also used to understand the normal function of genes.
The production of chemicals and enzymes for research and therapeutics requires cell factories for fermentation. Caribou Biosciences aims to improve microbial production strains for the production of therapeutic products. They are also using their technology to enable the bio-based production of materials never produced by microbes before, like fragrances, flavors, industrial cleaning products and products used in transportation.
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May 16, 2017