University of Helsinki
We all know what scissors do don’t we? How easy it is to cut away at a piece of paper and get your desired shape. Now imagine that the paper is actually a DNA molecule and that the scissors don’t quite go where you want them to. Or rather, you need to find a specific set of scissors for every kind of cut you wanted to make.
This is what molecular and genetic scientists have been dealing ever since the discovery of Restriction enzymes. They can cut genes at specific sequences, but they would have had to find a specific restriction enzyme for specific sequences, therefore the process of isolating a gene was painstakingly long. With CRISPR came the revolution!
Crispr was first identified in the Escherichia coli genome combined with CAS9. The latter of the two components isolates and cuts the gene in combination with RNA molecules. This was part of the adaptive immune system present in most bacteria, which allowed it to defend itself against viruses or plasmids.
The social implications of such a discovery are truly profound. As we all know, many “uncurable” diseases, such as Parkinson’s or Alzheimer’s have a genetic cause. Even hair loss in men is genetic! With all of this in mind CRISPR could really forge a new path in gene therapy, making it tailored and certainly more effective. But how could this life changing therapy be delivered to patients? The most common method used is AAV vectors: Basically, small viruses that inject the material into target cells. Doctors could either modify the cells ex-vivo (outside of the patient) and insert them later, or simply in-vivo (inside the patient).
As of today, only ex-vivo therapy has been tested and has proved successful for cancer immunotherapy for instance. That said, it is still very limiting as it cannot be applied to many diseases that would need in-vivo therapy. But why hasn’t this been possible so far? The issue with the latter is our immune system. While the CRISPR mechanism is part of the bacteria’s defence system, our body doesn’t recognise it as its own, therefore it attacks it and destroys it. Like a bunch of lose computer parts won’t make a computer, a bunch of lose genetic material doesn’t prove effective in curing diseases. Yet, one in-vivo therapy has proved successful in inverting some forms of blindness!
The issues with CRISPR aren’t few. You should also consider that for now it hasn’t proved too precise with an accuracy of under 50%. Although CRISPR editing in humans remains a highly debated and controversial topic, a few Regulatory Affairs Certification (RAC)-reviewed and FDA-approved CRISPR gene therapy trials have opened after thorough consideration of the risk to benefit ratios. These first few approved trials, currently in Phase I/II, are only for patients with severe diseases, such as cancers or debilitating monogenic diseases. The outcomes of these trials will dictate how rapidly we consider using this system to treat less severe diseases, as the risks of the technology are better understood.
Sources:
Uddin, F., Rudin, C. M., & Sen, T. (2020, June 30). CRISPR gene therapy: Applications, limitations, and implications for the future. Frontiers. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01387/full%C2%A0
Rodríguez-Rodríguez, D. R., Ramírez-Solís, R., Garza-Elizondo, M. A., Garza-Rodríguez, M. D. L., & Barrera-Saldaña, H. A. (2019, April). Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (review). International journal of molecular medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414166/%C2%A0