CRISPR and Gene Editing Technology

Introduction and connection to sts

Gene editing is a group of technologies that give a scientist the ability to alter an organisms existing genome. This type of technology exhibits a rather revolutionary way of manipulating genes that can have a wide variety of clinical and therapeutic applications.  CRISPR technology stands for a Clustered Regularly Interspaced Short Palindromic Repeats and it was originally discovered through studying adaptive immune responses in bacterial models. CRISPR is a type of genome editing naturally occurring in these types of bacteria. Today, scientists are utilizing this template to modify and edit strands of DNA in living organisms. This means that CRISPR technology is a type of gene editing, a revolutionary way of manipulating genes that can have a wide variety of clinical and therapeutic applications. Some examples of applications include treatments for blindness and certain cancers, and could even be used to create rapid disease testing like for Covid-19 (Science & Tech Spotlight: CRISPR Gene Editing, 2020).

Gene editing technology has a very notable connection to STS for its potential of treating a wide variety of diseases.

CRISPR-cas9 and other gene editing technologies have the potential to revolutionize disease therapy and drastically improve patient outcomes, but many ethical considerations must be taken in order to ensure safety and efficacy.

Understanding CRISPR Technology

In 1987, CRISPR Technology was discovered in the immune system of archaeal genomes as a form of natural adaptation to defending microbes from bacteriophage infection (Ishino 2018). Another repeat genomic sequence was discovered in Haloferax mediterranei in 1993. Studies in the 2000s concluded that the CRISPR-Cas (CRISPR-associated) system gave immunity against bacteriophages through spacer sequence observations. It is believed that CRISPR models applied to humans and other organisms can be used to target viral infections.

At the core of CRISPR technology lies the CRISPR-Cas9 system, which is the tool derived from a bacterial immune system. The system contains the Cas-9 enzyme and a strand of guide-RNA, more commonly known as gRNA. The molecular guide, gRNA, directs the Cas-9 enzyme towards the target molecular strand of DNA. Once at the target location on the DNA strand, the enzyme essentially acts as a pair of molecular scissors and cuts the desired strand. This allows scientists and researchers to effectively delete, insert, or modify a specific strand of DNA, virtually acting as a natural DNA editing tool.

Images

Figure 1: CRISPR depicted as the “molecular scissors for gene editing”

Figure 2: Visual Depicting Mechanism of CRISPR-Cas9 System

Applications in Disease Therapy

CRISPR has the potential to treat a wide range of diseases, from rare genetic conditions to more common ailments like cancer and cardiovascular diseases. Utilizing the defense mechanism of observed bacterial immune systems, CRISPR can create new pathways of engineered microorganisms for disease therapy.  It allows for permanent modification of a genomic target sequence that could potentially repair DNA damage (Rodriguez-Rodriguez 2019). The creation of such can be manipulated to induce certain responses in programmed mutation. CRISPR can have applications in metabolic engineering, disease therapy, agriculture, and biomedical sciences. With the recent Covid-19 outbreak, CRISPR can be applied to Covid testing and treatment. Much of CRISPR’s popularity comes from its high effectiveness and success rates. It is a form of genome editing that does not cause lethality to any organism.

Gene editing technologies, like CRISPR,  are headed for clinical trials. These trials will consist of ex vivo experimental testing, a way of testing a patient’s cells outside of the patient’s body. This is opposite of in vivo testing, which takes place within the patient. This will allow a safer form of testing that will not result in any unintended consequences like off-target editing. It ensures that the gRNA will guide the enzyme to splice the correct location on the DNA strand before reintroduction into the patient’s body (Hirakawa 2020). Further translation from lab bench experiments into a more clinical setting is needed to fully realize CRISPR as a substantial form of disease therapy.

Ethical Considerations and Challenges

With CRISPR being at the forefront of genome editing, it is no surprise that it raises ethical questions since it is an advanced form of biotechnology. Is it ethical for gene editing technology, like CRISPR, to genetically alter human DNA? Gene editing can have consequences such as unintentional changes in the genome. Other issues that groups point to are “designer babies” with enhanced genetic traits as potential unethical outcomes of this technology. There are also environmental concerns as gene editing could disrupt the natural selective pathway all organisms have taken to survive. Worldwide legislation must be unanimously agreed upon regarding the growth of gene editing technology in order for it to be used for only the betterment of the human race (Ayanoglu 2020).

CRISPR Technology has several limitations that may prevent its immediate commercialization. These limitations include immunotoxicity, DNA Damage/Apoptosis, or off -target effects. A common problem with CRISPR technology is specifically the off-target effect, which is when the Cas-9 enzyme cleaves a different site on the DNA strand than intended. After sufficient investigation, researchers suggest that the amount of gRNA and Cas-9 must be optimized and proportionate, and must be completed through direct delivery (Joshi 2024). This will ensure that the system is not thrown out of balance and will only target the intended sequence. The ethical considerations and technological challenges present many hurdles for CRISPR to overcome in order for it to be fully realized in a clinical setting.

Conclusion

CRISPR gene editing is extremely new and use of this technology must be approached pre-cautiously.. It represents a groundbreaking advancement in the field of gene editing, offering unprecedented precision and efficiency in targeting specific genes. Its potential to revolutionize disease therapy cannot be overstated. A lot of research studies at this point can have conflicting evidence regarding its safety and efficacy. Current and accepted information could be subject to change in the coming years as research is ongoing. And it goes without saying that grounded ethical guidelines must be established to further the technology. The responsible use of CRISPR technology is paramount, and ethical considerations must guide its application. With continued dedication and ethical vigilance, CRISPR technology has the ability to usher in a new era of personalized medicine, where genetic disorders or diseases are no longer a barrier to health and well-being.

References

Ayanoğlu, Fatma Betül et al. “Bioethical issues in genome editing by CRISPR-Cas9 technology.” Turkish journal of biology = Turk biyoloji dergisi vol. 44,2 110-120. 2 Apr. 2020, doi:10.3906/biy-1912-52

Hirakawa, M., Krishnakumar, R., Timlin, J., Carney, J., & Butler, K. (2020, April 9). Gene editing and CRISPR in the clinic: Current and future perspectives. Portland Press.

Ishino, Y., Krupovic, M., & Forterre, P. (2018). History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing

Technology. Journal of bacteriology, 200(7), e00580-17. https://doi.org/10.1128/JB.00580-17

Joshi, S., Verma, D., & Gupta, R. Kr. (Eds.). (2024). CRISPR-Cas System in Translational Biotechnology (First edition.). Elsevier Inc.

Rodríguez-Rodríguez, D. R., Ramírez-Solís, R., Garza-Elizondo, M. A., Garza-Rodríguez, M. L., & Barrera-Saldaña, H. A. (2019). Genome editing: A perspective on the application of CRISPR/Cas9 to study human diseases (Review). International journal of molecular medicine, 43(4), 1559–1574. https://doi.org/10.3892/ijmm.2019.4112

Image Sources

“Science illustration show CRISPR – Cas 9 work for cut and edit DNA genetic sequence as novel technique of molecular engineering.” by trinset on Adobe Stock.

“Illustration depicting CRISPR molecular scissors for gene editing.” by TopMicrobialStock on Adobe Stock.

AI Acknowledgement

ChatGPT was used in the Conclusion Section. The following prompt was used:

Write a conclusion paragraph to an essay about CRISPR technology using these guidelines:
– Summarize the key points discussed, emphasizing the potential of CRISPR technology in gene editing and disease therapy.
– Emphasize the importance of ongoing research and ethical considerations in harnessing the full potential of CRISPR.
– Conclude with a hopeful outlook for the future of CRISPR technology and its potential to transform healthcare and improve patient outcomes.

Andrew used some of the sentences the AI generated for more cohesive structure and flow of these sections.