Is CRISPR Causing Concern?
Since its discovery in 2012, the gene editing tool CRISPR-Cas9 has generated quite an excitement by making the possibility of routine genome editing a reality. A number of biotech companies, including CRISPR Therapeutics, Intellia Therapeutics, Editas Medicine, and eGenesis, are currently developing medicines based on this technology. In addition, CRISPR-based technology is already being used in the clinical context in China. For example, at Hangzhou Cancer Hospital, immune cells of patients with oesophageal cancer are being reengineered to fight the disease.
But lately an article published in Nature Biotechnology has led to a debate over the safety of the potential CRISPRbased therapies. Studies have highlighted that CRISPR-Cas9 edited cells might trigger cancer. It is likely that this finding can drastically affect the accuracy of gene editing and cause alterations of non-target genes, leading to concerns that if used clinically, CRISPR-Cas9 gene editing could result in unwanted damage in humans, or worse, tumor formation.
“CRISPR technology is a powerful technology in gene editing and could answer a lot in the field of genetic disorders. However, we do not yet fully understand gene interactions and that could only come with new knowledge which is being generated. We need to gather enough evidence through experiments before reaching any conclusion”, shares Dr N K Ganguly, Former DG, Indian Council of Medical Research.
The major safety concern is that, this field is moving so quickly and some researchers want to get into human clinical trials right away, even before the CRISPR technology paradigm has been fully validated. Researchers in China have actually proceeded to human clinical trials using CRISPR much faster than has been possible in the United
States. Recent reports state that somewhere between 80 and 100 people are already being tried, or already being tested using CRISPR.
“Much of the basic research around the CRISPR-Cas9 system has centered around two themes. The first has been to ensure specificity of the system so that the modifications are made only in the desired genomic region and not anywhere else in the genome. The second theme centres on the nature of modification. Knocking out a gene by causing doublestranded DNA breaks is the most common technique, but the system is very versatile and it has been used for everything from gene editing to controlling gene expression. These techniques continue to be optimized and the costs have reduced to a point that has democratised research in the field. However, the implications of carrying out these changes in humans are far from clear”, points out Dr Vamsi Veeramachaneni, Chief Scientific Officer, Strand
No matter which side wins, it is evident that years will go by before the CRISPR system is ready for prime time and clinical use. “Fully achieving the promise of this technology will be achieved with more knowledge and understanding of the genomeediting mechanism supported by scientific peer review and the rigor and regulations applied to clinical trials”, mentions Supriya Shivakumar, Head of strategy, Gene Editing & Novel Modalities, Merck.
However, the safety concerns surrounding CRISPR-based gene editing are less of a concern in potential agricultural applications in which the technology could also have important implications.
“This technology has tremendous potential in agriculture and manipulations in Synthetic Biology. Beneficial effects in corn, potato and tomato have already been shown. The biggest problem could still be regulation, especially in India. India needs to move fast in terms of ushering in a second green revolution using such technologies in a transparent manner. It should not get into the muddle being experienced with the application of GM technology. A pro-active initiative to draw guidelines for use of CRISPR and its commercialization in agriculture is a priority. An early success in producing Betacarotene-rich banana in India is a distinct possibility”, highlights Professor G. Padmanaban, NASI Platinum Jubilee Senior Scientist, Department of Biochemistry, Indian Institute of Science (IISc).