Written By Anika Nair
11 years ago, scientists Jennifer Doudna and Emmanuelle Charpentier first described a new gene-editing technique known as CRISPR. Since then, it has been gaining attention all over the world for its ability to change the genetic makeup of organisms, especially with the new sickle-cell treatment that was approved by the Food and Drug Administration on December 8th. But how does this impact the field of neuroscience? Before we go into that, let’s talk about the mechanisms of CRISPR technology.
What is CRISPR?
CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, provide bacteria and archaea with immunity to fight viruses and other entities, basically serving as the immune system for bacteria and archaea (Jinek et al., 2012). CRISPR creates a blueprint which allows enzymes to change the DNA present in certain cells. Using this approach, scientists transcribe CRISPR segments into RNA, which includes a guide sequence that can match existing DNA in a person’s body. With this guide sequence comes enzymes such as Cas-9 that can attach themselves to the DNA and make cuts or alterations to the DNA. The ability of CRISPR to make these small changes in human DNA reveals a lot of potential in future genetic disease treatments.
CRISPR’s Impact on Neuroscience
In addition, CRISPR has shown a lot of promise in neuroscience research. In 2021, Brown University neuroscientists shared how they were using CRISPR to examine the genes that impact nervous system function. They revealed that CRISPR expands the ability of researchers to study diseases in model organisms and stem cells, allowing them to understand the mechanisms of neurological disorders on a deeper level. Additionally, the use of CRISPR technology has been linked with the obstruction of amyloid precursor protein (APP) in Alzheimer’s Disease and the deletion of exon portions in the Dmd gene in Duchenne muscular dystrophy, aiding in the prevention of both disorders (Kuruvilla et al., 2018)
Current Concerns about CRISPR Technology
Although there is much potential for the future of CRISPR technology, there are quite a few concerns associated with it. One of the biggest challenges are OTEs, or off-target effects, which are essentially unintentional genetic modifications (Uddin et al., 2020). Although there have been attempts at reducing OTEs, including creating Cas9 variants to minimize their effects, there is large variability in the efficiency of these strategies. Furthermore, CRISPR alterations have often resulted in apoptosis, or cell death, rather than the intended gene edit, signifying concerns in CRISPR-based gene therapy.
Future Hopes
While we still need to learn more about the scope of CRISPR technology, it holds a lot of potential in disease treatments, especially for neurological diseases. For example, CRISPR systems have allowed researchers to efficiently study the workings of schizophrenia, which involves many genes and is very complicated. Although it is not certain when CRISPR technology can be used directly in neurological disease treatments, there is definitely hope for its impact in expanding our knowledge of neuroscience, serving as an important and crucial breakthrough in neuroscience research.
References
CRISPR Gene Editing 101. (2023, April 25). Cleveland Clinic. https://health.clevelandclinic.org/crispr-gene-editing
Feijo, S., Communications, Manager, O., & Science, C. I. for B. (2021, April 22). How Brown neuroscientists are using CRISPR to accelerate brain research — and more. Brown University. https://www.brown.edu/news/2021-04-22/crispr-neuroscience
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science, 337(6096), 816–821. https://doi.org/10.1126/science.1225829
Kuruvilla, J., Sasmita, A. O., & Ling, A. P. K. (2018). Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases. Neurological Sciences, 39(11), 1827–1835. https://doi.org/10.1007/s10072-018-3521-0
She, A. (2016, April 6). CRISPR in Neuroscience: How Precision Gene Editing May Unravel How the Brain Works (and Why it Sometimes Doesn’t). Science in the News. https://sitn.hms.harvard.edu/flash/2016/crispr-in-neuroscience-how-precision-gene-editing-may-unravel-how-the-brain-works-and-why-it-sometimes-doesnt/
Uddin, F., Rudin, C. M., & Sen, T. (2020). CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Frontiers in Oncology, 10(1387). https://doi.org/10.3389/fonc.2020.01387
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