Guide RNA scans DNA to find the target sequence to which it binds. Cas9 then engages with the DNA and cleaves both strands at the target site. (Image: Interpreted from Intellia Therapeutics by Alma Popescu).
Caribou Biosciences is a biotechnology startup based in Berkeley, CA, that provides technology-based solutions to cellular engineering. They are one of the leading companies developing the novel CRISPR-Cas9 technology, which is rapidly becoming the next big thing in genetic engineering. CRISPR-Cas9 or Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9, is derived from the adaptive immune system of prokaryotes. It was discovered that prokaryotes have the ability to remember past viral infections by incorporating viral nucleotide sequences into their genome. These sequences are copied into short RNA molecules, known as guide RNAs, which search foreign DNA that invade the cell until they find a match. Once a match on the DNA is found they guide a programmable nuclease Cas-9 to the site allowing it to engage with and cut the foreign DNA, thereby destroying the virus. In addition, the CRISPR-Cas9 system can be adjusted for use in genetic editing and can even be used in mammalian cells.
By creating different guide RNA sequences it is possible to design an easy to use, effective, precision genetic editing tool that can cleave at any site in a genome. Once the genome is cut, host DNA repair machinery can be utilized in order to introduce genetic changes such as insertions or deletions of genes. By combining this technology with knowledge of the genome, the applications of the CRISPR-Cas9 system are far reaching. This is why Caribou has formed strategic alliances with companies in research, agricultural biotechnology, industrial biotechnology and therapeutics.
Genetic engineering has come a long way since its inception, and many of the current tools being used are focused around nucleases such as Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs) and of course CRISPR-Cas9. Both ZFNs and TALENs work on a similar principle to each other – they are both proteins which recognize and bind DNA via a DNA binding domain and cut DNA using a nuclease domain. As their specificity comes from a DNA binding domain, a new protein domain must be designed and created for each new target site on a genome. However, a big advantage of CRISPR-Cas9 technology is that its specificity depends only on a short guide RNA molecule which is far easier to design and more inexpensive to create than a protein domain. The CRIPSR-Cas9 system is also efficient, easy to use and can target multiple sites on a genome at the same time by using multiple guide RNAs. No wonder Craig Mello, who shared the 2006 Nobel Prize for medicine, said “CRISPR is absolutely huge. It’s incredibly powerful and it has many applications, from agriculture to potential gene therapy in humans”. Craig Mello, University of Massachusetts Medical School, received the Nobel Prize for a previous genetic discovery known as RNA interference.
Amongst Caribou’s co-founders are Rachel Haurwitz, who was named as one of Forbes’ “30 under 30” for science and healthcare in 2014 and Jennifer Doudna, who was awarded the 2015 Breakthrough Prize in Life Sciences for research on harnessing the bacterial CRISPR-Cas9 system for use in genetic engineering, which she shared with her colleague, Emmanuelle Charpentier.
CRISPR-Cas9 technology has really taken off in the last few years and the research being done at the Doudna lab, UC Berkeley, has played a pivotal role. Caribou’s technology is based on research being carried out by co-founder Jennifer Doudna and her colleagues, and at the core of Caribou’s IP protection is an exclusive license to the foundational CRISPR-Cas9 work from the University of California and the University of Vienna. The technology is so promising that together with Atlas Venture, Caribou Biosciences has co-founded the biotechnology company Intellia Therapeutics. Based in Cambridge, MA, Intellia develops therapeutic products using Caribou’s CRISPR-Cas9 technology as they hold an exclusive license to utilize Caribou’s Cas9 technology platform for the discovery, development, and commercialization of human gene and cell therapies. Since its inception in 2014, Intellia has already received $15 million in Series A financing led by Atlas Venture and Novartis and on 7th January of this year, signed a five year R&D collaboration with Novartis.
Caribou Biosciences is making leaps and bounds with their genetic editing platform. They entered into a collaboration with Novartis on January 7, 2015. It was reported that “Under the terms of the agreement, Caribou will receive funding for a one-year collaborative research program and Caribou will provide Novartis an option to non-exclusively license research use rights of the Caribou CRISPR-Cas9 platform”. In addition, last week Caribou announced that they secured $11 million in Series A financing from several investors including Fidelity Biosciences, 5 Prime Ventures, Mission Bay Capital and Jennifer Doudna herself. CEO Rachel Haurwitz spoke on behalf of Caribou “We are delighted to have attracted such an impressive group of investors that share our enthusiasm for the vast potential of our proprietary CRISPR-Cas9-based cell engineering platform”. Caribou have said they will use this funding to further accelerate deployment of their CRISPR-Cas9 technology – Watch this space!
Rachel Haurwitz, CEO of Caribou Biosciences will be speaking at SynBioBeta’s 2015 London Conference!
For more information, click here.