New Study Demonstrates Undesired Effects of CRISPR Gene Editing in Human Embryo

By T. Chakraborty, Ph.D.

Since the advent of clustered regularly interspaced short palindromic repeats (CRISPR), the genome-editing tool has advanced by leaps and bounds. It has found utilization in various aspects of biological research, from basic bench science to translational medicine. Very few technologies have advanced and impacted biological science in the last decade as much as CRISPR, so much so that the pioneers of the technology, Dr. Emmanuelle Charpentier and Dr. Jennifer A. Doudna was awarded the Nobel Prize in Chemistry this year.

Despite the success, the technology has its own limitations and controversies. One of the ethical questions that have left the scientific community divided is CRISPR’s probable use in human embryos. A recent study, published in the journal Cell by Dr. Dieter Egli and colleagues from Columbia University may have, for the time being, answered the question of safety and efficacy of using this technology in human embryos [1].

The Ethical Dilemma and Controversy

With the rapid advancement of CRISPR-Cas9, scientists worldwide have debated the potential use of this technology in human embryos to make genetically edited humans. This may be a revolution in the field as it may help reduce genetically inherited diseases like diabetes, blindness, among others. But with a lack of government funding for using this technology in humans, combined with skepticism from many scientists regarding the off-target effects, which can be potentially detrimental, this question has mostly remained unanswered.

In 2018, Dr. He Jiankui, from Southern University of Science and Technology in Shenzhen, China, claimed to have genetically modified fertilized embryos and gave birth to two genetically engineered babies. This claim met with a lot of criticism from the scientific community and the government leading to the firing and imprisonment of Dr. Jiankui for illegal medical practice.

The Study

In the study, the authors aimed to modify a mutation in gene EYS, which, when inherited from parents, can cause blindness in the offspring. The group used CRISPR to make a double-stranded break in the chromosome, which will help repair the mutation in the zygote. To their surprise, 50% of the double-stranded breaks were not repaired, which led to the loss of chromosomal arms in the zygotes. Further, the off-target effects of CRISPR-Cas9 led to complete chromosomal loss in zygotes, thereby demonstrating that the technology faces severe challenges for use in human embryos [1].

Dr. Egli, the corresponding author, referenced Dr. Jiankui’s work and said, “If our results had been known two years ago, I doubt that anyone would have gone ahead with an attempt to use CRISPR to edit a gene in a human embryo in the clinic. Our hope is that these cautionary findings should discourage the premature clinical application of this important technology but can also guide responsible research to achieve its ultimate safe and effective use.”

Ethical Debate and the CRISPR Industry

In a couple of papers published in the CRISPR Journal, Dr. Doudna sided with most of the scientific community that the technology should not be used in human embryos. Any off-target mutation in embryos is potentially detrimental as the defect may carry over to the next generation. Further, 75 countries already have legislation in place against genetically modifying human embryos, which may make it possible to come to a consensus of not applying this nascent technique in humans [2]. Dr. Egli commented, “This study is not going to stop the field. But we have to ask what to do with these powerful tools, and in which context they are safe and efficacious.”

Though the use of CRISPR for diagnostic purposes and model developments in the pharmaceutical industry, this study leaves a huge question mark on the various CRISPR-based treatments in clinical trials. There is a need to investigate the long-term effects of CRISPR-based therapies in humans. With multiple pharmaceutical giants, including Merck, Vertex Pharmaceuticals, among others investing billions of dollars in CRISPR based therapies for the treatment of Duchenne muscular dystrophy, cancer, and other diseases, it will be interesting to see the effect of this study on future investment decisions. Cambridge-based pharmaceutical company CRISPR therapeutics, who pioneers in CRISPR-based treatments, have already seen a 5% decrease in stock value since the publication of the study.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: The Future of CRISPR: Three Areas The Nobel Prize-Winning Tech Will Be Most Impactful

References

1. https://www.cell.com/cell/fulltext/S0092-8674(20)31389-1#%20
2. https://www.wsj.com/articles/crispr-gene-editing-can-lead-to-big-mistakes-in-human-embryos-11603983608

Author

Tulip Chakraborty