By : Eva Mamane
CRISPR Mechanism
What is CRISPR?
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a novel technology that allows scientists to delete or replace DNA - the hereditary information that carries our genes - with a high degree of specificity.
The CRISPR/Cas9 system has many implications in disease treatment, in the agricultural field, and many other realms. In 2020, Nobel laureates Emanuelle Charpentier and Jennifer A. Doudna were awarded The Nobel Prize in Chemistry “for the development of a method for genome (genome = all the genetic information in an organism) editing” (Callaway, Ewen et al.).
So how does CRISPR/Cas9 work?
Pieces of DNA from a bacteriophage (virus) are inserted into the cell. Those pieces of DNA get transcribed into RNA bound by something called tracrRNA. The RNA (from the virus) bound to the tracrRNA is together termed crRNA (Roy, Richard). Cas9 (enzyme - acts like DNA scissors) recognizes this tracrRNA and is brought to other DNA segments that crRNA recognizes. This crRNA brings the Cas9 “scissors” to a part of the genome, cuts the DNA near the target sequence and the artificial RNA sequence is glued in (Roy, Richard).
So in short, they are cutting out the segment of DNA they want to remove, and replacing it with the gene they added into the cell (or they can simply just remove or just insert a segment of DNA)!
CRISPR Applications
The burning question: What are the practical applications of such a powerful tool?
There are several ingenious applications of CRISPR/Cas9, one of them being in the agricultural domain.
In agriculture, it helps to more efficiently target healthy seeds. Some of the gene-associated characteristics that can be ameliorated include higher yields, tolerance to drought, longer shelf-life and better nutrition (Pioneer Seeds United States).
Through the CRISPR/Cas9 system, the location in the genome that codes for these genes is targeted, either editing, deleting or replacing DNA sequences. CRISPR can also improve disease resistance of the plants and reduce the amount of time needed to develop seeds - saving time and money (Pioneer Seeds United States). This advancement in agriculture can help accommodate the flourishing human population!
CRISPR and diseases…
Many diseases are caused by mutations(when a nucleotide -A,C,G, or T- is mistakenly changed to an incorrect nucleotide) in the genome, generating aberrant proteins (DNA is transcribed into RNA, then translated into proteins). CRISPR can be used to both identify the mistake, and to replace the mutated gene with a normal gene (Henderson, Hope).
Some of these CRISPR-treatable diseases include Sickle cell Anemia, Cystic Fibrosis, and Huntington’s disease (Doudna, Jennifer). Moreover, many diseases caused by viruses (like Hepatitis B) are very hard to treat, but with CRISPR, HBV (Hepatitis B Virus) can be entirely removed from the genome (Abudayyeh, Omar)!
CRISPR/Cas based viral vaccine development
CRISPR can increase the rate of vaccine development. CRISPR effectively increases the vaccine production yield by getting rid of unwanted genes that give rise to viral infections or diseases (Bhujbal S, Bhujbal R, Giram P).
CRISPR: Philosophy and Ethical Considerations
What about when not to use CRISPR?
One of the most frequently considered ethically dangerous uses of CRISPR is editing the germline (Doudna, Jennifer). Things like cancer are mainly caused by mutations in somatic cells (all the non-reproductive cells in the body, the cells that aren’t inherited). Germline cells on the other hand are heritable cells (cells from sperm and egg). Editing the germline raises several pertinent questions. Would the future generations from this organism consent or approve of being developed with the use of CRISPR technology? What if there is a mistake in the CRISPR process?
Additionally, how do we determine who can use CRISPR to ensure it only falls in the right hands, and how do we effectively create and enforce CRISPR-related laws in an unbiased manner? How do we even ethically determine who can ethically determine what is and isn’t allowed with CRISPR? There would also certainly be large corporations putting pressure on CRISPR researchers, causing a potential unethical usage of CRISPR.
While most people may agree that treating diseases is acceptable for CRISPR and that using it for eugenics or cosmetology is crossing the line, what about treating something like color blindness? The essential question is: Where do we draw the line and how do we clearly define the line so that there is absolutely no ambiguity (both legally and ethically) with the applications of CRISPR? (Piergentili, Roberto et al.)
Evidently, CRISPR is a fascinating, revolutionary tool in the scientific field with a myriad of practical and much sought-afterapplications. But this can be a dangerous weapon for humanity if not wielded carefully. We must, as a species, self-reflect on the future of humanity, to ensure that CRISPR brings us light without burning us. How do you envision a positive future for CRISPR?
Works Cited:
Ayanoğlu, Fatma Betül et al. “Bioethical issues in genome editing by CRISPR-Cas9 technology.” Turkish journal of biology, vol. 44,2 110-120. 2 Apr. 2020, doi:10.3906/biy-1912-52
Bhujbal, Santosh et al. “An overview: CRISPR/Cas-based gene editing for viral vaccine development.” Expert review of vaccines, vol. 21,11 (2022): 1581-1593. doi:10.1080/14760584.2022.2112952
Henderson, Hope. “CRISPR & Health.” Innovative Genomics Institute. 2022, https://innovativegenomics.org/crispr-made-simple/crispr-health/
Ledford, Heidi et al. “Pioneers of revolutionary CRISPR gene editing win chemistry nobel.” Nature review, 7 Oct. 2020, https://www.nature.com/articles/d41586-020-02765-9
Loike, John D, and Rabbi Tzvi Flaum. “CRISPR Technology: A Jewish Legal Perspective.” Rambam Maimonides medical journal, vol. 13,4 e0029. 27 Oct. 2022, doi:10.5041/RMMJ.10487
Piergentili, Roberto et al. “CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues.” Cells, vol. 10,5 969. 21 Apr. 2021, doi:10.3390/cells10050969
Pioneer Seeds United States. “CRISPR-Cas for Healthy Seed Development.” YouTube, 2018
Sufian, Sandi et al. “The Dark Side of CRISPR.” Scientific American, 16 Feb. 2021, https://www.scientificamerican.com/article/the-dark-side-of-crispr/
UC Berkeley. “The ethics of CRISPR gene editing with Jennifer Doudna.” YouTube, 30 Nov. 2015
WebMD. “CRISPR and the End of Genetic Diseases.” YouTube, 18 May 2021, https://youtu.be/IhTVdfJzy4g
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