A game-changer in genome medicineAugust 12, 2020
Molecular scissors for genome editing and their use in therapeutic approaches are likely to be a major game changer in how we look at next-generation genomic medicine. The evidence so far demonstrates the significant value of such therapeutics in dealing with human diseases. One such system is CRISPR/Cas9, which provides a new tool or platform for manipulating regions of the cancer genome, metabolic diseases and infections. Tremendous advances in the three different genome editing tools — zinc finger nucleases (ZNFs), TALENS and CRISPR/Cas9 — have paved the way for translational research that impacts clinical practice. The first report of genetic editing was reported in 2017 when Brian Madeux, an American with Hunter’s syndrome, received treatment at Benioff Children’s Hospital at University of California-San Francisco, where ZNFs were delivered using AAV vectors. This clearly shows the importance of gene editing in a clinical perspective for several diseases. In cancer therapy, a combination of gene editing and immunotherapy can be the next big goal as CAR T cell therapy has officially been approved for clinical use in 2017. CLL and ALL patients respond very well to CAR T cell therapies targeting CD19. The US FDA has recognised this as a breakthrough therapy for leukaemia and lymphoma. This positive outcome of CAR T therapy in clinical trials of B cell malignancies has generated enormous enthusiasm for improved therapies and hope for cancer patients. Once commercialized, this technology can generate a new set of pharmaceutical and biotechnology companies in the field. However, this is still in its infancy and prohibitively costly for a large segment of the population. Therefore, commercialisation will depend a lot on how these therapies become more affordable. Even though the off-target effect of genome editing needs major research, this technology has led to improved understanding and development of tools for gene expression regulation epigenetics, therapeutic drug development, cell imaging and diagnostics. Further optimisation and innovation by integrating nanotechnology may bring this field much closer to clinical applications in the near future.
Precision medicine, which depends on targeted drugs for a specific gene fragment or protein, can also be improved, particularly as the usual therapy eventually leads to certain mutations at the active or drug binding site. However, using CRISPR/Cas9 technology, scientists have established a mammalian, genome-wide gRNA library. This gRNA library can be an ideal tool for drug screening or targeted screening of specific pathways. The establishment of such gRNA libraries can reveal changes in gene expression after cancer drug therapy and help investigate drug-gene/protein interactions by incorporating small molecules for perturbation. This can help identify novel targets for precise treatments and enable better precision medicine. It is, therefore, reasonable to believe that genome editing can bring new hope for several aspects of medical care, such as therapies, diagnostics, and further exploration of biological mechanisms. This field is going to be a game changer and genomic medicine is going to script the next era of therapeutics for humankind.