The start of 2015 brought news from Novartis that it had signed an agreement with Intellia Therapeutics and Caribou Biosciences to license its proprietary CRISPR/Cas9 gene editing platform to develop novel treatments for chronic genetic-based diseases.
The start of 2015 brought news from Novartis that it had signed an agreement with Intellia Therapeutics and Caribou Biosciences to license its proprietary CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing platform to develop novel treatments for chronic genetic-based diseases. Intellia is a private Massachusetts-based biotechnology company cofounded in November 2014 by Caribou and Atlas Venture to develop new therapies for inherited diseases using Caribou’s proprietary CRISPR/Cas9 platform.
Under the 5-year agreement with Intellia, Novartis gains exclusive rights to develop all collaborative programs using Intellia’s CRISPR platform to engineer chimeric antigen receptor (CAR) T-cells ex vivo. Together, Novartis and researchers from the University of Pennsylvania have already been evaluating CAR T cells in the oncology setting and have reported positive preliminary results from early phase trials conducted in patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia. Jeff Lockwood, global head of communications, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, explained that, “The ability to gene edit CAR-Ts gives us the opportunity to potentially broaden the application of CAR-T therapy. Selective gene targeting allows us to explore allogeneic CAR-T approaches and modulate the efficacy and tolerability of CAR-T therapy.”
The agreement also commits Novartis to working with Intellia on developing targets for ex vivo editing of hematopoietic stem cells (HSCs). However, the agreement does not prevent Intellia from pursing its own pipeline of HSC-based therapies. Findings from successful in vitro experiments that used CRISPR/Cas9 to edit genes in HSCs suggest the platform might have strong potential in the development of HSC-based therapies for hereditary blood disorders like sickle cell anemia or hemophilia.
In Novartis’ agreement with Caribou, Novartis agreed to fund a 1-year collaborative research program and make additional undisclosed investments in exchange for nonexclusive licensing rights to use the Caribou CRISPR/Cas9 platform. In a press release, Novartis said its agreement with Caribou is “focused on using Caribou’s foundational CRISPR platform and intellectual property as a research tool for drug discovery.”
The CRISPR/Cas system is an immune defense mechanism first discovered inStreptococcus pyogenesbacteria. Various bacteria and archaea (another type of single-celled microorganism) use the CRISPR/Cas system to defend themselves against invading viruses and foreign DNA. A few different CRISPR systems have been identified, but the one currently generating the most enthusiasm among researchers is the type II CRISPR/Cas9 protein complex, sometimes dubbed the “molecular scissors” approach. Cas9 is an RNA-guided enzyme that cleaves double-stranded DNA at specific sites in the genome upstream of a protospacer adjacent motif (PAM).
The DNA sequence for every gene has a complementary RNA sequence, and scientists Jennifer Doudna and Emmanuelle Charpentier found a way to program guide RNA to direct Cas9 to highly specific DNA sequences in a cell targeted for editing. Cas9 triggers DNA repair within the cell and can be used to knockout a gene, insert or delete a gene, or even introduce a random mutation. The CRISPR gene editing platform is a cheaper, faster, easier method of gene editing than earlier platforms, and it allows more precise targeting. Doudna and Charpentier have won several accolades for their efforts to unravel the mysteries of CRISPR, and some have speculated a Nobel Prize may be in their future.
Since CRISPR/Cas9 was discovered, it has been studied in several commonly used research organisms, including yeast, zebra fish, flies, nematodes, and mice. In 2014, researchers at the Massachusetts Institute of Technology (MIT) used CRISPR to treat a mouse model of type I tyrosinemia, a condition that results from by a mutation in the gene that codes for the FAH enzyme. The MIT group used guide RNA and Cas9 to deliver a template containing the correct DNA sequence for the FAH gene to cells in the liver. The complex succeeded in inserting a copy of the correct gene into several hepatocytes, which replicated themselves and ultimately replaced enough diseased liver cells to cure the mice.