Industry Info / Mentee Updates

Gene Editing: An Inevitable Future

By Anisha Bellur, Walnut High School, Walnut, CA 91789, Class of 2020

Edited by Caitlyn Kellogg, University of Southern California, Class of 2017

 

What Exactly is Gene Editing?

Genes are made of DNA and provide the code for protein synthesis. During DNA replication, due to environmental factors or coincidence, changes, or mutations, may occur in the DNA. This may result in alterations to the new strand being synthesized. Gene editing is when mutations such as insertion, deletion or replacement of DNA are induced by scientists at a specific DNA site in order to engineer a new DNA sequence of their choosing1.

 

Is Gene Editing a New Technology?

No, gene editing is not new and has been used by scientists for several decades in yeast, bacteria, mice, zebrafish, and other organisms in order to study physical traits and disease. Gene editing has also been used in the agriculture and livestock industry2. Although gene editing is not new, CRISPR technology is. Although this new gene editing technology has made gene editing faster, cheaper and more efficient, it has fueled concerns over the ethics of gene editing.

 

What Exactly is CRISPR?

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene editing machine that has the ability to insert specific sequences into DNA. CRISPR can work in many types of cells. Targeted sites can be customized to include certain DNA sequences2. Unlike its predecessors, CRISPR can change one specific gene out of thousands. Additionally, while previous gene editing machinery could not permanently edit DNA, CRISPR can introduce permanent DNA changes.

 

What is the Inspiration Behind CRISPR?

 CRISPR was developed based on similar cellular machinery in the bacteria Streptococcus pyogenes that protects the bacterial DNA from viral infections. The technology was developed at the Broad Institute, the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard Medical School, Harvard University Faculty of Arts and Sciences, and the Massachusetts Institute of Technology (MIT) by scientists George Church, David Liu, Ph.D., and Feng Zhang Ph.D.

Early CRISPR didn’t require perfection because when CRISPR originally came out, it was not intended for humans. However, on November 30th, 2014, The #Broad Institute, #Harvard University, #MIT and #Editas Medicine have entered into a worldwide licensing agreement to develop human therapeutic applications of CRISPR.

 

What are the Unknowns for Gene Therapy?

There are three major issues involved in gene editing. First, will the mutation be able to treat or even cure a disease? Second, what are the possible undesirable side effects that may arise due to the delivery method of the mutation or due to the mutation itself? Lastly, how will germline mutations impact future generations1?

 

How about Germline Gene Editing?

 In 2015, scientists tested CRISPR in human embryos; although they were able to introduce mutation, the genetically modified embryos were not able to grow to their full extent1.

When gene editing occurs in the somatic genome, the progeny (daughter) of those somatic cells carry the mutation as well. During germline genome editing, however, both the offspring cells and offspring of that organism may be affected because the germline contributes to gamete (egg and sperm) formation1. Germline editing makes eugenics, or the selection of desired traits to be passed on to future generations, possible. Negative eugenics is removing the traits that are not desired, while positive eugenics selects for certain beneficial traits1. Current experiments allow an embryo to develop from a genetically edited sperm or egg; however, the embryos are not allowed to grow for more than a few days and are not implanted into a woman.

 

How can We Perform Gene Therapy Safely?

There are many regulations and rules regarding human embryo research and how human embryos can be used. These guidelines reflect ethical principles like beneficence, or inflicting the least harm possible to reach a beneficial outcome, and justice1. Oversight is helpful because it creates transparency between the public and the researchers by ensuring researchers adhere to a known set of guidelines1. Conducting gene therapy research with ethical behavior, complete transparency and consideration of the effect on all involved parties (including the patient, family and society) will help avoid unintended consequences.

Completely halting government support for embryonic gene therapy research only puts our country behind others, makes gene editing less safe for us and makes us dependent on others’ technology. In 2001 George Bush restricted embryonic research in the United States while other countries continued their stem cell research1. Currently, the Food and Drug Administration (FDA) prohibits any clinical trials involving genetic modifications that can be inherited.

 

Impact on Society and Concerns Related to Eugenics (Ethical Viewpoint)

The introduction of CRISPR to the medical field creates concerns related to social justice and equal access to technologies. Contrary to popular belief, CRISPR will not likely result in the loss of genetic diversity in the entire population. Instead, it will have a treatment effect within selected subgroups, such as subgroups of Down Syndrome individuals who may have cardiac defects that could be deadly1.

Some believe that CRISPR may result in a competition to become “the best human” and others believe that scientists might be overstepping the line and playing God. However, human genome editing might be less offensive than other medical approaches such as prenatal testing and selected pregnancy terminations.1

Additionally, genome editing may exacerbate societal health care disparity. Genome editing is likely to be expensive, access is likely to be limited, and it may not be covered by all payers and health systems. This can create large differences in the availability of genome editing in different geographic regions, ethnic groups, or socioeconomic groups. This can result in diseases being more prevalent in certain socioeconomic classes, locations and cultures. Additionally, less genetic disease overall may lead to less priority placed upon the treatment of genetic disease, and may affect the availability of resources to those struggling with genetic conditions.1

 

Conclusion

Through gene editing, researchers have gained a better understanding of the function of genes and how to manipulate them. With this great power, many medical, economic, social and ethical challenges have appeared, and many others may arise in the future.

Even though there are methods to determine the effects of accidentally mutated genes (off target genes), these methods have not been standardized and the safe amount of mutations in a gene is not known; in addition, the analysis of a single person’s genome is not sufficient and studies should be done on the effect of off target mutations in a collection of genomes that represent a genotypically diverse group of people. Until we have a better understanding of the outcomes of gene editing, it is important to proceed carefully and think broadly and scientifically.

 

#CRISPR #embryo #genetherapy #gene editing #USC #WalnutHighSchool

 

References

  1. Ormond, K.E., Mortlock, D.P., Scholes, D.T, Bombard, Y., Brody, L.C, Faucett, W.A, Garrison, N.A, Hercher, L., Isasi, R., Middleton, A., Musunuru, K., Shriner, D., Virani, A., Young, C.E. (2017). Human Germline Genome Editing (ASHG Position Statement) The American Journal of Human Genetics 101, 167-176.

 

  1. Ormond, K.E., Mortlock, D.P., Scholes, D.T, Bombard, Y., Brody, L.C, Faucett, W.A, Garrison, N.A, Hercher, L., Isasi, R., Middleton, A., Musunuru, K., Shriner, D., Virani, A., Young, C.E. (2017). Human Germline Genome Editing https://www.ncbi.nlm.nih.gov/pubmed/28777929

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