Mutations in DNA are responsible for many genetic diseases and developing ways in which we could ‘reverse’ such changes has been on scientists’ radar for years. Thankfully, there was a breakthrough in this research area with the discovery of CRISPR-Cas9 technology by Prof. Jennifer Doudna in 2012. This powerful gene editing technology gives us a new perspective on treatment of various diseases, such as sickle cell anemia and maybe even cancer. In this article, we will get to know how this technology was developed, how it works, and its potential uses.
THE DISCOVERY OF CRISPR-CAS9
It all starts with bacteria. Bacteria are often invaded by viruses which is why they need to have a way of developing immunity to them. CRISPR is a perfect solution. In short, if a virus infects bacteria, a small part of its RNA is integrated into bacterial DNA. That’s when a Cas nuclease comes in and cuts the DNA at the two points where it connects with RNA. That snippet of RNA is used as a basis for building immunity of bacteria against the virus. Guide RNA (gRNA) created by bacteria is complementary to the viral RNA, and when the virus invades the bacterial cell the next time, gRNA localizes the viral RNA sequence incorporated into DNA and ‘guides’ Cas nuclease to cut it.
THE USE OF CRISPR-CAS9 FOR MEDICAL TREATMENT
We now know where this technology comes from, but how do we use it for gene-editing purposes? Well, let’s take a quick look at a standard use of CRISPR to fix a mutation in a gene.
First, scientists need to develop guide RNA complementary to the mutation in DNA. That gRNA will show a Cas enzyme where it has to cut the DNA.
When gRNA binds to DNA at a right place, our genetic scissors, Cas nuclease, cut DNA at two points to get rid of the mutation. Those two points are called double strand breaks (DSBs)
after we remove the faulty base sequence, scientists can use other technologies to repair that fragment of DNA
There are many advantages to this clever mechanism. It’s fairly ‘simple’, yet very precise and flexible; with the use of CRISPR-Cas9 we can not only change but also add or remove different genes. What’s even better is that it’s cost efficient.
THE USE OF CRISPR-CAS9 IN MEDICAL TREATMENT
As you can expect, the idea of editing the human genome with this technology has been quite controversial. It will take a long time before CRISPR will be used on a daily-basis in the treatment of various genetic diseases. So far, it’s been only used in life-threatening cases where there were no other options to offer to patients. Moreover, we can’t edit germline cells with CRISPR because all changes would be passed onto future generations. Nevertheless, we are on the right track to create safe treatment options with CRISPR which will save many lives.
Michael Le Page. (2020). What is CRISPR? New Scientist. https://www.newscientist.com/definition/what-is-crispr/
Synthego. (2019). The Ultimate Guide To CRISPR: Mechanism, Applications, Methods & More. Synthego.com. https://www.synthego.com/learn/crispr
YourGenome. (2022, February 8). What is CRISPR-Cas9? @Yourgenome · Science Website. https://www.yourgenome.org/facts/what-is-crispr-cas9/
(2022). Biointeractive.org. https://www.biointeractive.org/sites/default/files/biointeractive/images/crispr-thumbnail.jpg