Gene Therapy for Mutation Repair as a Cancer Treatment Strategy

The advent of CRISPR/Cas9 is making gene therapy so much cheaper and easier that uses previously rendered impractical are now more plausible to attempt. For example, cancers are driven by a very wide range of mutations, such as those disabling cancer suppression genes. A possible approach is to develop a stable of gene therapies that repair those mutations when they are present, starting with the most common, and thus shutting down cancer cells and halting their growth. The large number of different genes and mutations to target has meant that this strategy would make little sense without the large reduction in the cost of building and deploying gene therapies that CRISPR has created. The challenge of uptake of a gene therapy into cells, how to guarantee that near all cells in a tissue have their genes modified, is still not yet solved, but that will come in the next few years - everyone in the field needs a solution to that problem in order to proceed, and so all eyes are upon it.

CRISPR/Cas9 is likely one of the most revolutionary tools in biotechnology, with tremendous implications for a broad range of biological and medical disciplines. As programmable scissors this technology allows cleavage of DNA at predefined sites in the genome of cells. Now researchers have found a way to utilize the technology to diagnose and inactivate cancer mutations, thereby accelerating cancer research. "Mutations in cancer cells are identified at increasing speed through next generation sequencing, but we mostly do not know, which of these mutations are actually driving the disease and which ones are rather benign." The authors first analyzed how many of the more than 500,000 reported cancer mutations could theoretically be targeted and found that more than 80% of the mutations could be cleaved with the currently most popular CRISPR/Cas9 system. The research group then demonstrated that they could specifically cleave a panel of common cancer mutations without significantly targeting the healthy, wildtype alleles.

Moreover, expression of Cas9 together with the cancer-specific guide (g)RNAs was able to unmask mutations that drive cell growth and viability in cancer cell lines. "This is an important advance, because we can now rapidly separate driver from passenger mutations. This is currently a bottleneck in cancer research. Because each cancer shows a specific combination of many mutations, this scientific approach could improve cancer diagnostics as mutations that promote cancer growth could be specifically identified. Based on the obtained results an individualized therapy could be initiated.


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