From a young age, we were taught that DNA, or deoxyribonucleic acid, was the holy grail of instruction manuals in our body and that it determined how we looked and acted. We grew up thinking that DNA was a permanent fixture of ourselves that couldn’t be touched, an instruction manual that couldn’t be fiddled with. While watching classic sci-fi movies such as “X-Men” and “Jurassic Park”, films where organisms can be genetically engineered with ease, we have probably at least once thought about the possibility of there being such a revolutionary scientific tool that exists.
In case you haven’t, let’s do that right now. Imagine a world where any precise location in your DNA sequence could be easily cut by a certain enzyme. Imagine a world where “bad genes” in a person’s DNA strand could be identified and removed for a lower cost than popcorn prices at the movie theater. A world where we get to witness the end of human genetic disease as we know it.
What we are anticipating here can easily be labeled as the stuff of science fiction. What we are anticipating is the CRISPR-Cas9 method for genome editing.
In the 1980s, scientists observed a strange pattern in the bacterial genome of E. coli. Between repeats, one DNA sequence would repeat itself with unique sequences. Scientists called this “clustered regularly interspaced short palindromic repeats”, otherwise known as CRISPR (4). In 2007, Rodolphe Barrangou and his colleagues discovered that CRISPR was a part of an immune system used by bacteria to defend themselves from viruses. The unique sequences in between the repeats turned out to be the DNA bits of dangerous viruses that bacteria used for future recognition. The other part of the system consisted of CRISPR-associated genes called Cas, one of which was Cas9, an RNA-guided endonuclease enzyme with the ability to snip out DNA.
How exactly does this system work? When the bacteria detect the presence of a virus, it creates two short strands of RNA, one which contains a DNA sequence that matches that of the virus. The two strands of RNA form a complex with Cas9. When the guide RNA which contains the matching DNA sequence to that of the virus finds its target within the viral genome, Cas9 cuts the viral DNA sequence, disabling the virus (6).
Recently, researchers have discovered a way to utilize this method in other organisms. They found that the CRISPR method could be engineered to edit the DNA sequence at a precise location. Dr. Feng Zhang and his team at MIT tested the CRISPR method on mice. They initially studied the gene MeCP2, whose mutations can cause Rett syndrome in humans, resulting in issues with language, learning, and coordination in girls. Taking their experiments a step further, they simultaneously tested the system on the genes Dnmt3a, Dnmt3b, and Dn.1.. Their results showed that more than 75% of the Dnmt3a and Dnmt1 genes were knocked out and no longer functioning in the cell (1). In the end, the mice get to live another day and that may mean another millennium for us humans.
What does this all mean for us? For a long time, scientists have been able to thoroughly study and understand the DNA sequence in cells. DNA sequencing has helped scientists identify the order of nucleotides in a DNA molecule and therefore find thousands of genes that affect our risk of disease. The question about whether there was a technology that could efficiently edit the DNA sequence and trim the bad genes that remained, that is, until the introduction of the CRISPR-Cas9 method. The CRISPR method can be utilized to change the DNA sequence and correct mutations that would otherwise have led to disease. Once the system recognizes a malfunctioning sequence in the DNA, the guide RNA, along with the Cas9 enzyme, work to cleave the sequence, disabling the mutation. Additionally, we can also–sometimes–insert a new and correct DNA sequence in place of the old one (2).
When using CRISPR appropriately, CRISPR can knock out the risk of genetic diseases such as cystic fibrosis (a disease that damages the lungs and digestive system) and Huntington’s disease (a disease where nerve cells break down). Going back to one of my previous statements, this can mean another millennium for us, as CRISPR is capable of putting an end to genetic disease once and for all by cutting out bad genes and disabling dangerous mutations. CRISPR also provides benefits for the fields of ecology and agriculture, as it can kill off disease-spreading insects and invasive species and improve crops and livestock by modifying genes (6). What’s even better, the reported cost for using CRISPR is only $30.
As with every rising technology, there has been some concerns about the use of the CRISPR method and its potential drawbacks (3). Some question the morality behind manipulating DNA in the body and its contribution to the possibility of human cloning. Additionally, ethical implications arise regarding whether CRISPR should be used in eggs, sperm, or embryos, where the modified DNA can then be passed on to following generations. Others also fear that dangerous, uncontrollable bacteria may be accidentally produced from this process (2).
The CRISPR-Cas9 method is a revolutionary system that can tremendously benefit not only human society, but also the world around us. Although CRISPR applications on humans are a rather far way off, there is room for improvement. When CRISPR does make itself commercially available to humans, with caution, CRISPR will be among the best breakthroughs in medical, ecological, industrial, and agricultural fields, greatly improving our world and society.
References and Footnotes
1) Davis, Kyle. CRISPR probes the inner workings of the genome in real time. National Human Genome Research Institute, May 2015. Web. 20 Jan. 2016. <https://www.genome.gov/27560763>
2) Fridovich-Keil, Judith. Gene editing. Encyclopedia Britannica, January 2016. Web. 20 Jan. 2016. <http://www.britannica.com/topic/gene-editing>
3) News Office. MIT, Broad scientists overcome key CRISPR-Cas9 genome editing hurdle. MIT News, December 2015. Web. 24 Jan. 2016. <http://news.mit.edu/2015/overcome-crispr-cas9-genome-editing-hurdle-1201>
4) Reis, Alex. CRISPR/Cas9 and Targeted Genome Editing: A New Era in Molecular Biology. Reagents for the Life Sciences Industry | NEB, 2014. Web. 23 Jan. 2016. <https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology>
5) Rubenstein, Irwin. Genetic engineering. World Book, 2016. Web. 20 Jan. 2016. <http://worldbookonline.com/student/article?id=ar220270&st=crispr#tab=homepage>
6) Zhang, Sarah. Everything You Need to Know About CRISPR, the New Tool that Edits DNA. Gizmodo, May 2015. Web. 20 Jan. 2016. <http://gizmodo.com/everything-you-need-to-know-about-crispr-the-new-tool-1702114381>