Embryonic Genomic Engineering

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Embryonic Genomic Engineering

Genomic editing is a hot topic in precision medicine today. Through the use of technology, individuals in the healthcare field are able to modify live genomes. Many of these genomes are modified during the embryonic stage of development, also known as gametic editing. With the discovery of CRISPR-cas9, genome editing possibilities began to take off. CRISPR-cas9 is a system in the human body's immune response that “cuts” the DNA of invasive pathogens to protect bodily cells from harm. A group of researchers discovered in 2012 that this tool could be used to target specific sequences in the human genome in order to alter its structure and, ultimately, function [1]. CRISPR has been at the forefront of gene editing since its discovery, but other methods have also been developed. With more research being conducted on this topic, the possibilities with this new technology are becoming clear. It is possible to modify genomes in order to slow disease progression, cure diseases, and even change an individual's phenotypic characteristics. This technology has numerous applications, ranging from curing diseases like HIV to allowing parents to select certain characteristics for their offspring. The window of applications has only just begun for this biotechnological process and has the potential to progress significantly in the near future.

As this technology advances, bioethical concerns become a topic of discussion. How far can new genomic engineering technology be taken? Is it acceptable to allow parents to select characteristics for their children? Is it permissible, on the other hand, to edit genomes in order to make an individual resistant to a disease? Given that some of these editing processes occur during the embryonic stage of a fetus, is it acceptable to carry out these procedures in the absence of consent from the individual being edited? All of these questions, along with many others, are of debate in the field of genomic editing. This page discusses the methods, technology, and ethical implications of genomic engineering, particularly with regard to embryonic or germline editing.

History

Many advances have occurred over the years, bringing us to where we are today in the field of genomic editing. There are several genome editing technologies available, including ZFNs, TALENs, and CRISPR-cas9 [2]. CRISPR-cas9 has been at the forefront of genetic engineering since its discovery due to its higher precision rates and self efficiency when compared to other methods. CRISPR principles were discovered by researcher Francisco Mojica in 1993. In the discovery of this locus, “this finding led him to hypothesize, correctly, that CRISPR is an adaptive immune system” laying the groundwork for today's genomic editing technologies [3]. Following this, by the 2000s the necessary technology had been developed and the human genome was sequenced allowing for gene editing technologies to be researched more efficiently. Around 2012 to 2013, researchers such as Virginijus Siksnys and Feng Zhang discovered that CRISPR-cas9 could be used as a genetic engineering tool to target specific genes in the human genome [4]. CRISPR-Cas9 is now being used in embryonic gene editing and in clinical settings for targeted therapies. The field of genomic editing is still in its early stages, but with the advancement of healthcare and computational technologies, it will inevitably take off.

Somatic Gene Editing

Non-reproductive cells in the body are changed by somatic editing. This method only targets a specific gene in a single cell type. Changing this gene has no effect on other cells in the individuals' bodies. After somatic editing, the edited gene will remain within this individual and will not affect the genes of their future children.[5][6]

Germline Gene Editing

Germline editing is done on "early-stage embryos, gametes (eggs and sperm), or germ cells that are the precursors of gametes" [7]. As a result of this, every cell in the embryo contains a copy of the edited gene. After this editing has occurred, there is the potential that the edited gene will be passed down to future generations. This is due to the fact that every copy in the embryo contains the edited gene, even sperm and egg cells. [8]

Germline genome editing processes are becoming more accessible in clinical settings than they were previously. Somatic genetic editing has already been approved in a number of clinical settings, making human trials with targeted therapies possible. This is because the editing is more controlled and the effects are restricted to the individuals being edited. Germline editing, on the other hand, has more unknown effects, increased factors, and more unethical implications. Since every cell in the individual has this edited mutation, it is difficult to determine what other unintended effects this induced change may have had. Currently, “any clinical trial proposals for germline alterations will be rejected by the Recombinant DNA Advisory Committee (RAC) of the NIH” [9]. Opposition to these laws is punishable by a fine, imprisonment, or both. In 2019, Jiankui He, a Chinese researcher, went against these guidelines to perform germline genomic experimentation. Jiankui used CRISPR technology to cause embryonic genetic changes that removed HIV-causing genes. His experiment was successful, but the ethical implications of using genomic editing technologies to interfere with human reproduction were controversial. “Going against rules and doing such research is forbidden by the international biomedical community” [10]. Although unethical, the results of this experiment revealed significant implications for the impacts of germline editing in a clinical setting.