Collaboration with the National Organization for Rare Disorders (NORD) at North Carolina State University
One of the hottest topics in science right now is CRISPR technology. Clustered Regularly Interspaced Short Palindromic Repeats are a group of DNA sequences that allow scientists to alter the genome. Before this huge development, certain genetic defects and predispositions were unavoidable. Now, with the power to edit what makes us who we are, there are a plethora of uses in agriculture and medicine. Here, we’ve collaborated with the National Organization for Rare Disorders (NORD) at North Carolina State University to talk about the role of CRISPR in cancer therapy.
Before we dive into cancer therapy, we need to discuss the mechanism behind CRISPR. How is this able to edit genes? Dr. Jennifer Doudna, the co-inventor of CRISPR technology, and recent Nobel Prize laureate from UC Berkeley describes this phenomenon. She examined that bacteria readily acquire a sequence of other species’ DNA into their own, in specific areas that we now call CRISPR (Jinek et al. 2012).
“When we studied the biochemistry of this system, it led to a kind of transformational discovery for us, which was that this system could actually be re-engineered as a single guided system.”Dr. Jennifer Doudna
CRISPR was synthesized by linking together two guide RNA sequences into a format that would provide the target information and a structural handle. This would lead them to their DNA targets and is used to modify multiple genes simultaneously. In this way, we have learned to artificially re-engineer bacteria’s natural system by using dual RNA guided programmable enzymes (Jinek et al. 2012).
So if we’re able to successfully modify genes, and cancer is often the result of gene anomalies, could we use this technology to treat cancer?
The first trial of CRISPR used in cancer research began at the University of Pennsylvania in 2019. The study tested a type of immunotherapy in which patients’ own immune cells are genetically modified to better kill their own cancer (Stadtmauer et al. 2020).
The therapy involves making four genetic modifications to T cells (immune cells that can kill cancer). It basically adds gadgets to T cells to fight cancer. One of these gadgets is a synthetic gene that gives the T cells a protein that can identify cancer cells better. CRISPR is also used to mute three genes that limit the cells’ cancer-killing abilities (Stadtmauer et al. 2020). With these limiting genes removed, the T cells are less inhibited to fight cancer.
CRISPR gives us hope to potentially “fix” the gene anomalies that lead to cancer. However, scientists need to first locate these genetic faults that have strong connections to cancer development. Dr. Jesse Boehm from The Eli and Edythe L. Broad Institute might have the answer to decipher the genetic landscape of cancer cells and use that to our advantage.
Dr. Boehm is the scientific director of the Broad Institute’s Cancer Dependency Map Initiative and an institute scientist at Broad. One of his main accomplishments is the development of the Cancer Dependency Map. This is used to analyze cancer cell lines and systematically identify genetic anomalies that are associated with cancer (Boehm et. al, 2015). These gene anomalies are mass targeted with the help of none other than CRISPR.
“CRISPR is such a sharp tool, it inspires a lot more confidence than its predecessors.”Dr. Jesse Boehm
The Map is most useful in identifying gene anomalies that contribute to rare cancers. But obtaining such cancerous tumors for research is difficult. This is where organizations such as Pattern and the Rare Cancer Research Foundation (RCRF) come into play. These sister groups perform a matching program that enables patients to directly donate their tumor tissue and medical data to research. All the data generated by the project is freely available to the research community and is dedicated to open science.
“Using Pattern, the Broad Institute of MIT and Harvard has created over 40 next-generation de-identified cancer models. These models and associated data will be shared within the worldwide research community.”Barbara Van Hare, Director of Foundation Partnerships at RCRF.
CRISPR has proven to be a powerful tool in the development of cancer therapeutics. The main drawbacks are the potential unwanted off-target effects and edits of this technology. It is still a long way from being a cure but is one of our first promising weapons against cancer.
What do you think of this modern gene-editing device? Do you think modifying our genetic makeup is medicinally important? Are we really on the brink of a genetic cure for cancer? Let us know in the comments below!
Boehm JS, Golub TR. An ecosystem of cancer cell line factories to support a cancer dependency map. Nat Rev Genet. 2015 Jul;16(7):373-4.
M. Jinek, K. Chylinski, I. Fonfara, M.Hauer, J.A. Doudna, E. Charpentier, A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 337 (2012), pp. 816–821.
Stadtmauer, E. A., Fraietta, J. A., Davis, M. M., Cohen, A. D., Weber, K. L., Lancaster, E., … & Tian, L. (2020). CRISPR-engineered T cells in patients with refractory cancer. Science, 367(6481).
Tsherniak, A., Vazquez, F., Montgomery, P. G., Weir, B. A., Kryukov, G., Cowley, G. S., … & Meyers, R. M. (2017). Defining a cancer dependency map. Cell, 170(3), 564-576.