By Dr Tomislav Meštrović, MD, PhD
CRISPR and Cas proteins have become a crucial tool for genetic manipulation in biomedical research and biotechnology, and the crux of its action is the recognition of specific sequences in the DNA and their subsequent cleavage from the chain. One specific system, CRISPR-Cas9, has become the standard for genetic editing, since it can be tailored to target any set of DNA sequences. Thus it is of no wonder that it caused an upheaval in biomedical field.
Nevertheless, it must be noted that the use of CRISPR/Cas9 carries enormous possibilities to further advance the human health and well-being, which is the reason why this system is being researched in a myriad of different human diseases – including cancer and HIV/AIDS infections. Still, as it is the case with any new technology, the benefits of CRISPR/Cas9 are followed by equally huge risks from potential misuse, but also unforeseen consequences.
Ethical concerns and safety issues
Akin to other emerging technologies in biomedical research, human genome editing opens some serious questions regarding equality and justice, for example who will have access to potential treatment and for whom those treatments will be developed. Therefore before CRISPR/Cas9 technology moves forward with clinical applications, ethical and safety concerns should be addressed.
Swift proliferation of germline editing therapies using CRISPR/Cas9 technology would undoubtedly bring a nontrivial risk. Therefore, this approach should be adopted into clinical practice only after appropriately paced review, similar to an ethical inquiry takes place. Regulation seems to be the most feasible approach, although some experts opt for temporary moratorium and laissez-faire approach.
One of the biggest risks of germline editing therapy is the introduction of alleles with unforeseen side-effects that would be recognized generations after initial gene editing. This is the reason why such therapies must be vetted by institutional regulators and funding bodies, with adequate verification of modifications in model cell line to ensure normal propagation rates of DNA introduced into the genome.
Moreover, any germline modification should offer unambiguous benefits to the patient. The technology should address monogenic disease that have no alternative treatment option, or widespread diseases for which embryo loss via prenatal genetic diagnosis and treatment will minimize embryo loss during germline modification research.
Current guidelines and considerations
A regulatory framework for human germline CRISPR/Cas modification should be introduced in order to meet both technical and ethical requirements inherent to these therapies. Such framework should strive to address unshaped safety mechanisms, augmented risk of multigenerational side-effects, ethical hurdles regarding human embryos, as well as any equity concerns.
Researchers in the United States are already addressing the necessity for regulation of human germline editing. At the end of 2015, the National Institutes of Health (NIH) still refuses to fund research proposals for CRISPR/Cas germline editing therapies. Nevertheless, it has to be emphasized that this policy does not automatically cover projects that are funded privately.
The International Summit on Human Gene Editing issued a statement on December 3rd 2015 that gene-editing technology should not be employed to modify human embryos intended for establishing a pregnancy. If a scientific consensus is reached that unviable embryos may be used for research purposes (in order to improve the efficacy of CRISPR/Cas system), lawmakers should evaluate novel guidelines regarding the funding and safety of genetic manipulation in these embryos.
In order to avoid fear-mongering, researchers will have to find a way to responsibly explain this technology to the general public. Caution and regulations are welcomed at the moment, but there is also a need for the development of prudent and well-timed set of guidelines – not only for the scientific community, but also for the humanity as a whole.
- Dhillon V. Genome Editing Systems. In: BioCoder #8: July 2015. O'Reilly Media, Inc., Sebastopol, CA 95472, 2015; pp. 59-66.
- Thakore PI, Gersbach CA. Genome Engineering for Therapeutic Applications. In: Laurence J, Franklin M, editors. Translating Gene Therapy to the Clinic: Techniques and Approaches. Academic Press, Elsevier, 2015; pp. 27-44.
Last Updated: Jan 13, 2016