The Era of Genome Editing: CRISPR and its applications
Gene or genome editing technologies are currently the hot topic in the main stream; however scientists, philosophers and science-fiction authors have been discussing its consequences and limits since the 1930s. As a researcher myself with a BSc degree in Biology, I’m faced with genome editing in an everyday basis. I still remember the first time I heard of it. It really sounded like a concept taken sci-fi movies! Before 2015, genetic engineering discussions remained at the theoretical level given the difficulty to “get genes to do as the human want”. It was during the last decade that the scientific community came up with several attempts to genetically modify genomes, but none turned out to be as efficient, precise and specific as the novel CRISPR/Cas9.
But what is “CRISPR”?
CRISPR (pronounced “crisper”) stands for Cluster Regularly Interspaced Short Palindromic Repeats and it was first discovered in archaea by Francisco Mojica in 1993 (Spain). To make a long story short, CRISPR constitutes the bacterial adaptive immune system.
It consists on a number of repeated sequenced of genetic code interrupted by DNA “spacer” sequences — remnants of viral DNA from previous infections. This spacer sequences are transcribed to RNA and, in case of a new viral infection, will target viral DNA. Once the viral target DNA is found, Cas9 — one of the enzymes produced by the CRISPR system — binds to the targeted DNA, cuts it and shuts it off.
“CRISPR serves as a genetic memory that helps bacteria to detect and destroy viruses when coming back.”
Although CRISPR has been known for long, we had to wait until 2013, when the Zhang lab published the first method to engineer CRISPR to specifically edit the genome in mouse and human cells, and therefore of any living organism. This revolutionary approach opened a new Era in genome editing much faster, cheaper and easier than ever before.
How is the CRISPR technology evolving?
The ability to add, remove or change DNA sequences is crucial to studies that investigate genetic disorders such as cancer, haemophilia or those rare diseases which we hardly heard about. However, the revolutionizing effect of CRISPR-Cas9 in genome engineering is such that nowadays it has been implemented in a multitude of model organisms and cell types in order to study not only genetic disorders, but to understand basic biological and/or developmental mechanisms.
Moreover, the CRISPR system itself has been engineered so that new enzymes with higher specificity or new functions are being developed, such as silencing or activation of specific genes, modification of RNA or new diagnostic tools.
What applications has the CRISPR technology?
Although revolutionary, CRISPR is a rather “young” technology which need refinement to fully implement it in our lives. As it happened before, the arrival of a new technology able to modify genomes in such a specific and precise manner has raised high expectations, especially in the field of medicine. Here these technologies are considered as a “holy grail”, since they promise the cure or chronic diseases by correcting mutated genes. Will genome editing be the best solution? It remains to be proved.
To date, CRISPR has helped to create animals for research that mimic human diseases, which promotes scientific knowledge towards a better understanding of such diseases and therefore the development of new treatments. But CRISPR promises much more than that. What if we could cure any genetic disease, what would it be? Here I offer you an example of some diseases that scientists are already targeting using CRISPR and that could potentially become the first to be treated by genome editing.
- Cancer is the prime example of genetic disorder, so much so that one of the first and more advanced CRISPR clinical trials, currently running in China (Hangzhou Cancer Hospital), is testing the potential of this technic in patients with advanced cancer of esophagus. So far, 86 patients have received this CRISPR treatment in China, and results will be available soon!
- Blood disorders such as beta-thalassemia, a blood disorder impairing the oxygen transport in the blood. The first CRISPR trial in Europe is aiming to edit haematopoietic stem cells to produce fetal haemoglobin, which binds to oxygen better than the adult haemoglobin.
- AIDS is caused by the HIV virus, and as such CRISPR could be used to cut the viral DNA out of the genomic DNA of the host’s immune cells. Another more controversial approach would be making us resistant to HIV infections. It is known that individuals with a mutation on the CCR5 gene are resistant to HIV infections. However, most of these applications are in very early stages of development, so clinical human trials will have to wait.
But CRISPR cannot only be used to cure diseases, also to diagnose them. This is the case of the SHERLOCK diagnostic tool. It works similar to pregnancy test: after dipping a simple paper strip in a processed sample, a line appears whether the genetic signature was detected or not.
“SHERLOCK provides an inexpensive, easy-to-use, and sensitive diagnostic method for detecting nucleic acid material — and that can mean a virus, tumor DNA, and many other targets.”
At the same time CRISPR technology can also be applied to the agricultural sector, where sooner or later will appear in the market as new products with desired traits, which the regulatory agencies might not be so reluctant as in the case of GMOs. The rapidly growing use of genome editing has human health and environmental safety considerations, therefore implementation of CRISPR in our day-to-day basis will take some time. How long should we wait to eat our first CRISPR meal?
