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Illustration by Yuree Chang

CRISPR: The gene editing technology revolutionizing biology

Headlines about gene-editing technologies like CRISPR promise agency over your own genetics as well as designer babies. Why is that future much further away than you may think?

Feb 29, 2020

CRISPR or Clustered Regularly Interspaced Short Palindromic Repeats, is a revolutionary gene-editing technology that scientists are using for diverse applications such as therapies for debilitating diseases, research into basic biological mechanisms and modifying crops for more attractive qualities like higher yield and disease resistance](https://doi.org/10.1038/s41438-019-0159-x). It is an exciting time to be involved in scientific research, but there is so much more we need to know to be able to efficiently and safely use the technologies we have. Moreover, the ability for scientists and mankind to become a designer of not only other organisms such as crops and lab mice, but also with humans raises huge ethical issues.
If we want to truly understand the implications of CRISPR as a technology, we first have to understand what it is changing. Your genome is the complete set of DNA in your body that serves as an instruction manual to make you, you. Everything from your eye color to your height is determined at least in part due to your genome. The instruction manual of DNA is written with four basic building blocks called nitrogenous bases - A, C, G, T. The information that is used to make all life is encoded in different combinations of these four bases. A sequence of these bases that has a functional product is called a gene. The term gene is thrown around in common discourse but is still not clearly defined by science. Some estimates qualify that only 2.94% of the human genome is made up of genes. This means that most of the 3 billion base pairs do not code for a specific gene product. Non-coding DNA can certainly be regulatory, but much more bioinformatic research must be done in order to understand the existence of this material in our genomes.
As genetics continue to define who we are, CRISPR can change that. Humans have been altering the genes of organisms for centuries through selective breeding. Since the discovery of DNA in the 1950s, people have made more controlled efforts to change the genetic material of humans and other organisms. There were many complicated and often expensive technologies developed by researchers to change the genetic code, but CRISPR has proven to be a cheaper and easier to use technology after being discovered in bacteria in 1987. CRISPR is a natural immune defense that bacteria have against viruses. CRISPR is often cited in relation to a protein called Cas9 or CRISPR associated protein-9. The Cas9 protein is the machinery that cuts DNA like a pair of molecular scissors and allows for gene editing to occur. The efficacy of this technology comes from its ability to target a specific sequence in the genome. This specificity arises from the inclusion of a guide RNA in the Cas9 complex. The guide RNA acts as a template by having a complementary sequence of bases to those that already exist in the genome. In 2012, CRISPR was adopted as a tool for research and has caused a completely new wave of biomedical research.
There are many diseases and disorders that are caused by genetic anomalies. More than 3,000 of the known genetic diseases are caused by a single base in the DNA. Many disorders are also caused by a combination or genetic predisposition and environmental factors. Researchers can use CRISPR to understand the particular mechanisms of this genetic predisposition by directly interfering with the DNA. This may lead to treatments later down the line for which CRISPR may be paramount.
Every cell in your body has a nucleus and each nucleus has DNA that encodes your entire genome. This means that in order to really change you, scientists would have to interfere with every one of the 37.2 trillion cells in your body. There are a few methods for getting around this experimental impossibility in practice. The first, which is accepted as a fairly safe therapy, is to extract specific cell types — commonly immune cells — and then reintroduce them into the patient. Another method is to edit the genome of an embryo, which is commonly referred to as the germ line. This would cause the change to be heritable for successive generations.
One researcher, [He Jiankui],(https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail) from China did in fact use this CRISPR method to edit a gene in human embryos which were then implanted into their mother’s uterus and carried to term. This action was not approved by any board of ethics and the researcher in question was sentenced to three years in prison as well as heavy fines. This type of long-lasting intervention will not be allowed until researchers know more about genetics in general, not to mention CRISPR itself.
A more legal CRISPR therapy was started in 2016 when the U.S. National Institutes of Health also approved clinical trials for a CRISPR cancer cell treatment. In this treatment, immune cells called T-cells were removed from patients and augmented for cancer-fighting with three basic edits. The results from these trials were first published this week and show no success in therapeutic ability, but they show promising results regarding the safety and feasibility for CRISPR in humans in the future.
Although we are starting to use CRISPR as a technology to use on humans and access to the tools of Cas9 and genome sequences may drive scientists to do some risky procedures and experiments, this is all highly regulated. Before intervening with the system, it is important that researchers understand how basic genetics work. We are in an era of incredible genetic advancement both in terms of understanding and technology. CRISPR can be used both in the discovery and research of genetics, but also in the installation of modulations — therapies — to this understanding. This duality allows CRISPR to be an invaluable tool if wielded with the right intentions.
For more accessible information on genetic engineering check out this video that goes through its history to ponder some [big ethical questions] (https://www.youtube.com/watch?v=4YKFw2KZA5o) to learn more about specific experimental applications of the technology.
Kit Palmer is a Columnist. Email her at feedback@thegazelle.org.
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