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From laboratory to clinic to environment: Top 5 ethical considerations in genome editing


Genome editing technologies are changing the way scientists approach the study, prevention and treatment of diseases. Rapid development of engineered endonuclease systems such as ZNFs, TALENs, and particularly CRISPR-Cas have made it possible to manipulate DNA with precision and efficiency at relatively low cost. These systems can be used to engineer the genomes of cells and help develop new therapies and technologies for human diseases. While these advancements open new avenues for research, they also promote important discussions about the applications and implications of these technologies for individuals, societies and the environment. Here are the top 5 ethical considerations in genome editing.



1. Somatic and germline genome editing


Genome editing systems can be applied to modify the DNA of two types of cells in an organism, somatic and germ. Editing the genome of somatic cells produces changes that only affect the individual whose cells are being modified. By contrast, germline editing introduces modifications in the genome of sperm, eggs and embryonic cells. Because these changes are heritable, they have the potential to permanently correct errors in the genome that are linked to genetic diseases. There are two main considerations about clinical applications of genome editing in germline cells. First, there are safety concerns. Current technologies may produce changes in non-target regions that may alter genome function in ways that have not been examined yet. Second, current genome editing platforms are not sufficiently efficient to ensure that genomic correction occurs before the cells divide. This may result in mosaicism, where some cells have the edited copy of a gene and others do not. Both considerations highlight the risks of prematurely applying genome editing to human therapies and become even more concerning if the technologies are used in germline cells. Nevertheless, recent developments in genome editing have improved systems with no off-target effects. Several therapies targeting somatic cells have entered clinical trials and show great promise for treating genetic diseases. However, more research is necessary until these technologies become safe to correct genetic errors in germline cells. In light of these considerations, scientists have called for a global moratorium to prevent any clinical use of germline genome editing.



Researchers have called for a global moratorium of germline editing until systems become safe for use in humans and specific regulations have been proposed to enforce ethical clinical applications of genome editing technologies.

Source: Getty Images


2. Genome editing research in embryos


The use of embryos in genome editing studies can expand our knowledge of human development and help improve systems for safe therapeutic applications. However, there are several regulations in place that limit research in embryos. Clinical applications of genome editing in embryos is currently prohibited in over 50 countries. In vitro studies of genome-edited embryos are permitted only up to the 14th day of development in several European countries, China and the USA, although not funded by the NIH in the latter. The UK and Sweden regulatory bodies even have specific regulations that prohibit use of genetically modified embryos, eggs and sperm for reproduction. Studies complying to these regulations have made great progress in improving genome editing systems for use in embryos. For instance, researchers have recently been able to successfully implement CRISPR-Cas9 in embryos to edit a gene associated with heart disorders, with reduced mosaicism and no off-target effects. This illustrates the importance of research in embryos and how it may help the development of therapies for hereditary diseases in humans.



3. Gene therapy and genetic enhancement


The applications of human genome editing are also an important topic for consideration. When applied for therapeutic purposes, these technologies aim to correct genetic errors or mutations associated with diseases. Several gene and cell-based therapies are being developed to treat disorders such as muscular dystrophy, sickle cell disease and cystic fibrosis. Others have entered clinical trials and show great promise for treatment of blood disorders and cancer. However, genome editing can also be used to improve function of normal genes. Ultimately, this could be applied to enhance characteristics that have a genetic component, such as intelligence, sociability end even physical traits. Genetic enhancement has been successfully used to select desirable traits in pets and livestock animals. While not as trivial, it poses important ethical concerns if applied to humans. Under certain circumstances, however, enhancement of genetic function may help to prevent development of certain conditions. This is the case of promising research in genes that could confer resistance to HIV. Scientists argue that genetic enhancement for disease prevention should be examined under different lens during ethical debate than genome editing for cosmetic purposes.



4. Societal and equity concerns


Genome editing therapies also have important ethical considerations for societies. This is particularly important if human germline editing becomes available for clinical use. Determining which genetic conditions should become the target of correction is one of great concern. Some disorders are devastating and severely impact a person’s quality of life. Others, do not affect a person’s ability to function and may even be mitigated through changes in lifestyle. In some cases, the ability to correct certain genetic disorders in embryos may even increase the social stigma on people living with those conditions. Another concern is determining how genome editing therapies will become accessible for patients. It is possible that these therapies would be expensive at first, requiring specific changes in healthcare systems to ensure equal access to treatment. Some genetic disorders are also more prevalent in certain regions of the globe than others. In this case, international cooperation may prove beneficial to bringing therapeutic developments to countries in need.



5. Gene drives and environmental impact


Gene drives are genetic elements in germline cells that can spread rapidly and alter the genome of natural populations. Recently, genome editing has been used to engineer gene drives in mosquitoes that act as vectors for malaria. These synthetic gene drives carry genetic modifications that make female mosquitoes sterile or inactivate genes required for the malaria parasite to grow. Genetically modified mosquitoes could help reduce wild vector populations and disease transmission, particularly in areas where access to treatment is poor. However, the consequences of releasing such organisms are unknown. The synthetic gene drives could lead targeted species to extinction and have catastrophic effects for ecosystems. Current small-scale experiments in the laboratory do not provide good predictions of potential outcomes. While tropical vector-borne diseases put several populations at risk, different approaches should be proposed to assess and monitor the impact of engineered organisms prior to releasing them into the environment.


Genome editing systems can be used to engineer gene drives with applications for human health and the environment.

Source: Esvelt et al. 2014. eLife


The future of human applications of genome editing


Experts in the field agree that several steps should be taken before genome editing becomes available for human applications. Informed discussion between scientists, government and public is necessary to assess and educate about the ethical, legal and societal implications of this technology. Communication between these different groups will help building guidelines and policies to support and regulate ethical research in genome editing. At the same time, policies and guidelines should provide the framework necessary for continuous research aiming to optimize genome editing systems for safe human and environmental applications. This joint effort is likely to promote the development of new therapies and help explore the benefits of genome editing technologies for human health.



References:

Carroll D. Genome editing: past, present, and future. Yale J Biol Med. 2017; 90:653-659.


Coller BS. Ethics of human genome editing. Annu Rev Med. 2019; 70:289-305.


Doudna J. Embryo editing needs scrutiny. Nature. 2015; 158:S6.


Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. 2015; 112(49):E6736-43.


Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y, Suzuki K, Koski A, Ji D, Hayama T, Ahmed R, Darby H, Van Dyken C, Li Y, Kang E, Park AR, Kim D, Kim ST, Gong J, Gu Y, Xu X, Battaglia D, Krieg SA, Lee DM, Wu DH, Wolf DP, Heitner SB, Belmonte JCI, Amato P, Kim JS, Kaul S, Mitalipov S. Correction of a pathogenic gene mutation in human embryos. Nature. 2017; 548:413-419.


Memi F, Ntoku A, Papangeli I. CRISPR/Cas9 gene-editing: research technologies, clinical applications and ethical considerations. Semin Perinatol. 2018; 42:487-500.


Plaza Reyes A, Lanner F. Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos. Development. 2017; 144:3-7.



About the author:

Eduardo Gutierrez is a recent PhD with a passion for research and science writing. He believes good communication can make science accessible and interesting for everyone. An evolutionary biologist by training, he has experience with molecular biology, sensory systems, and evolution, and is also interested in health and medical sciences.


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