Friday, 21 May 2021

The possible risks in applying genome-editing technology to human beings

Over the last decade, the exited development of genome editing technology has revolutionized research on the human genome, which has enabled investigators to better understand the role of a single-gene product to a disease in an organism. In the 1970s, the development of genetic engineering (manipulation of DNA or RNA) established a novel frontier in genome editing. Based on engineered or bacterial nucleases, genome editing machinery have been developed at a rapid pace over the past 10 years and have begun to show extraordinary utility in various fields, ranging from basic research to applied biotechnology and biomedical research.

 

 Figure source: BioEdge, February 04, 2019

 

Genome editing allows the specific modification of a genome; genes are modified within their respective location in the genome, making the changes often indistinguishable from natural mutations. Developments of this technology such as the use of gene drives, where specific genes are spread within populations, or the use of viral vector systems, are enabling additional applications in environmental engineering and disease treatment. There are substantial individual and societal benefits from applying genome editing; nonetheless the technology also poses significant risks to individuals, society as a whole and the environment.

Genome editing has big potential in human inheritable disease treatment and human enhancement. Recent examples that are currently undergoing safety testing in clinical trials are the use of somatic gene therapies involving immune cell modifications to treat cancer, CRISPR-based approaches to treating HIV, and the proof of principle of genome editing in the treatment of heritable diseases such as Duchenne muscular dystrophy. Key safety concerns in this area have been the number of off-target changes, mosaicism and potential epigenetic effects. These are not new safety concerns, but have also been encountered in other gene therapeutic approaches. The existing step-wise approach applied in clinical studies should therefore be sufficiently robust to identify, assess, and govern such risks.

Certain genome editing techniques open the possibility for the development of a new class of infectious pathogenic organisms. A recent example has been the creation of cancer models in mice, where the cancerous mutation was introduced through genome editing using viral vectors – in essence transforming cancer into a transmissible infectious disease. This creates novel safety risks that will need to be included in biosafety oversight schemes. In addition, such work has the potential to create new generations of biological and chemical weapons which might not be detectable by current diagnostics.

The use of genome editing in environmental engineering has been discussed in the context of pest control, with new ways to eradicate agricultural pests, as well as that of disease eradication. For example, gene drive systems are being developed to eradicate malaria, and contemplated for the eradication of the Zika arthropod vector. Key safety concerns relate to the environmental harmfulness, controllability and reversibility of such environmental interventions. Key security concerns relate to their potential use as socio-economic and environmental weapons.

The use of genome editing in agriculture for breeding purposes in plants and animals creates unique and novel challenges to biosafety and biosecurity. Key safety concerns relate to the outbreeding and spread of these new varieties into natural populations, the detectability of these new variants and challenges to established coexistence provisions.

Based on aforementioned statement, in this argumentative article, I will argue and explain two possible risks that are possibly occurred.

The first is the ‘off-target genome editing effect’. It refers to unintended and nonspecific genetic changes. Possibly, this occurs during the editing process because of some reasons (e.g., limitation of knowledge and human errors), leading to unwanted mutations happened. For instance, using CRISPR/Cas9 technology to treat cancer patients might accidentally promote unwanted changes in the genome derived from nonspecific banding of the CRISPR/Cas9 system to the DNA, potentially generating new diseases or complications and endangering patient’s life.

Reducing the number of off-target changes made during genome editing, which again is sequence dependent. For CRISPR-Cas9, use of a nickase is one way to improve specificity. That said, any off-target changes induced at the epigenetic level—alterations potentially affecting modified offspring later in life—also would require close monitoring.

Related:  

CRISPR/Cas Systems and Their Application for Genome Editing

Redesign of Terpenoid Biosynthetic Pathway in Plant by Genome Editing toward Human Health

The second is ‘gene drive’ or ‘genetic drive’. This is the downstream effect caused by off-target mutations. In detail, this incident occurs when unwanted mutations that possibly undetected by our current technologies or our knowledge are incorporated into the genome. Those genes are subsequently passed to many generations through the cross-breeding process. In another case, those genes can potentially be transferred onto other organisms in a population (i.e., through the horizontal gene transfer process). Once they become part of the cycle, those genes are then stable in the environment. Finally, those genome changes possibly cause various cases such as antibiotic resistance genes or other mutations that go out and stable in a population and would be very difficult to be controlled.

In short, there will always be dark and light sides, pros and cons in life. The precise use of this technology would become great solutions for solving diverse problems in human beings, in the other side, inappropriate use of this bio-machine will be harmful to human life. 

References:

https://www.nature.com/articles/nbt.3234

Rath J. (2018) Safety and Security Risks of CRISPR/Cas9. In: Schroeder D., Cook J., Hirsch F., Fenet S., Muthuswamy V. (eds) Ethics Dumping. SpringerBriefs in Research and Innovation Governance. Springer, Cham.

Li, H., Yang, Y., Hong, W. et al. (2020). Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Sig Transduct Target Ther 5, 1. 

 

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