Written by: Shreya Sharma
Genome editing is a technological process used to make alterations to DNA. These create changes in various physical traits, such as hair or eye colour, or decrease an individual’s risk of contracting certain diseases. Although there are many perceived benefits to the ability to alter preexisting DNA, there is widespread debate over its usage, especially as new technologies display greater accuracy and ease of use.
Genome editing technologies work similarly to scissors and cut the DNA at a specific point. After cutting, DNA can be added, removed, or replaced to create the desired sequences. The very first genome editing technologies were created in the late 1900s, which primarily used restriction enzymes. These are proteins that recognize short nucleotide sequences, known as the target sequence or restriction site, and cut the DNA at that exact location. Restriction enzymes are found and harvested from bacteria. DNA-digesting enzymes also exist within the human body, such as in pancreatic fluid, but these cut on a random basis and produce various heterogeneous fragments that are unusable for sequence editing.
In 2013, the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) system was created as a faster, more affordable, accurate and efficient gene-editing method, and is used by most current research scientists when editing genomes. This system was adapted from a naturally occurring bacterial process, but its application is very similar in the lab. RNA with a short guiding sequence is created to bind to the target DNA sequence, and it also binds to the CAs9 enzyme. The modified RNA recognizes the desired DNA sequence and cuts it. Then, the innate repair mechanisms of the cell are used to add or remove genetic material or replace it with the customized sequence.
Gene therapies are being developed to prevent and treat various diseases in humans, particularly those with genomic bases such as diabetes and cystic fibrosis. There are two broad categories of gene therapy: somatic and germline. Germline therapy alters the DNA of reproductive cells, causing the changes to be carried through generations. Comparatively, somatic therapies target cells that are non-reproductive and only affect the individual receiving the therapy. In 2015, somatic gene therapy was successfully used to help fight a one-year-old child’s leukemia. Rather than CRISPR, a different technology called TALENs (Transcription Activator-Like Effector Nuclease) was used. After trying many unsuccessful treatments, special permission was acquired to try to treat the child using gene therapy, and it saved her life. However, these are still experimental treatments due to the ethical and technological barriers to genetic editing.
Safety is one of the most prominent concerns due to the chances of mosaicism (some cells display the edit while others do not), or off-target edits. The general agreement in the scientific community is that until enough research is conducted to deem germline editing completely safe, it should not be used clinically for reproductive purposes. Many researchers further argue that genome editing may never offer enough benefits to replace existing processes such as in-vitro fertilization (IVF) or preimplantation genetic diagnosis (PGD). However, certain situations are best resolved by genetic editing. For example, if both parents are homozygous for a disease-causing variant, all of their children would be expected to have the disease as well, and the process of selecting viable embryos through PGD would be futile. There is also the concern that even therapeutic uses for genome editing can create a precedent that will lead to using gene editing processes for enhancement processes. Many argue that once proven safe enough, genome editing should be used medically to cure genetic diseases, while enhancement concerns should be handled through regulation and policies.
Informed consent is also an argument against germline therapy as the embryo and subsequent generations are affected, rather than the individual themselves. However, this argument is countered by the fact that parents are already making complex decisions that will affect their future children, including IVF and PGD. There are also moral and religious obligations to the use of embryos. Some countries have allowed research to be conducted on non-viable embryos - embryos that would not result in a live birth- while others have approved research to be conducted on viable embryos. The National Institutes of Health have not funded any form of genetic editing in embryos.
With all of the rapid advancements in gene-editing technology, it is important to have continuous discussions regarding the scientific, moral, and ethical issues surrounding these processes. Potential risks, but also the associated benefits, should be openly discussed to maintain transparency with society and keep everyone informed.
References
Genome Editing Pros and Cons. (2020, August 25). Retrieved August 31, 2020, from
https://www.leopoldina.org/en/topics/genome-editing/genome-editing-pros-and-cons/
What are the Ethical Concerns of Genome Editing? (n.d.). Retrieved August 31, 2020, from
https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns
What are genome editing and CRISPR-Cas9? - Genetics Home Reference - NIH. (n.d.).
Retrieved August 31, 2020, from
https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting