Image is courtesy of Genetic Literacy Project.
What is CRISPR?
CRISPR stands for "Clusters of Regularly Interspaced Short Palindromic Repeats." It alters DNA sequences and modifies gene function, and its potential applications include correcting genetic defects as well as treating and preventing the spread of diseases. The CRISPR protein can identify, cut, or insert specific DNA sequences, which is especially useful when it comes to researching COVID-19.
Of course, as with any genetic engineering technology, there are many ethical and legal considerations that CRISPR must address. Bioethicists and researchers strongly suggest that gene editing should be proven safe before being offered as a treatment option. Furthermore, everyone must have equal access to this treatment once it is available.
The Relationship between CRISPR and COVID-19
There were three identified ways to relate CRISPR with COVID-19. The first method uses CRISPR to edit the SARS-CoV-2 genome. This involves an approach called PAC-MAN (Prophylactic Antiviral Crispr in huMAN cells), which attacks the virus's genetic makeup and reduces the amount of virus by 90%. The second method takes the form of CRISPR-based COVID-19 Tests. In fact, a CRISPR based test was approved as early as May 8, 2020, by the FDA. Lastly, CRISPR can be used to develop herd immunity. The population's gene sequences can be edited using somatic cell editing and germline editing through this process. However, this procedure raises ethical concerns, as it decides the fate of future embryos.
CRISPR's COVID-19 testing technology has seen significant advancement. It allows the Polymerase Chain Reaction (PCR) testing of SARS-CoV-2 to be rapid, portable, accurate, and low-cost. The CRISPR-Cas 13a targeting gene can detect SARS-CoV-2 from a nasal swab RNA, and a mobile phone microscope can read the resulting report. This technology claims to return results from 15 to 30 minutes, in addition to estimating the viral load in the sample. Doctors use this to monitor the infection over time and assess how contagious the condition may be for the patient.
COVID-19 testing process using CRISPR technology (cell.com).
Cas13 proteins are programmed to identify the viral RNA of SARS-CoV-2. Then, they combine with a probe that turns fluorescent when cleaved (activation). The smartphone camera measures the fluorescence; the rate at which the fluorescence brightens is indicative of the viral load.
Daniel Fletcher, a bioengineer at UC Berkeley bioengineer and an investigator at Chan Zuckerberg Biohub, said that "when coupled with repeated testing, measuring viral load could help determine whether an infection is increasing or decreasing." This method requires neither the virus' RNA to be converted to DNA nor the DNA amplified. This saves a significant amount of chemical reagents and laboratory equipment.
The CRISPR diagnostic test for SARS-CoV-2 requires only a cell phone camera and a small darkened box (Daniel Fletcher).
Future Outlook
The scientific community is still pushing for answers to COVID-19, as they have been since the beginning. For example, Mammoth Biosciences has partnered with Agilent Technologies to work towards another machine that uses Cas12 enzymes to detect SARS-CoV-2's genomic sequences. The platform aims to process approximately 1,500 samples over eight hours. Soon, the company plans on submitting its test for an FDA emergency authorization. The team consists of scientists from UC San Francisco, UC Berkeley, Gladstone Institutes, and Jennifer Doudna, president of Innovative Genomics Institute. Doudna won the 2020 Nobel Prize in Chemistry for co-discovering CRISPR-Cas genome editing.
In the future, the smartphone-based diagnosis mentioned earlier in the article could also benefit from GPS and digital connectivity. This would allow scientists to track the spread of infections in various regions. "We hope to develop our test into a device that could instantly upload results into cloud-based systems while maintaining patient privacy, which would be important for contact tracing and epidemiologic studies," said Melanie Ott, director of the Gladstone Institute of Virology. Overall, upon pairing vaccines and CRISPR-based diagnosis, countries can expect an increased likelihood of removing lockdowns sooner.
References
Armstrong, M., Bhuiya, A., Boehm, D., Chen, P., Crawford, E., D'Ambrosio, M., Derby, M., DeRisi, J., Doudna, J., Fletcher, D., Fozouni, P., Gray, C., Harris, A., Joehnk, B., Kistler, A., Knott, G., Kumar, G., Langelier, C., Meyer-Franke, A., . . . Zhao, C. (2020, December 4). Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy. Retrieved from https://www.cell.com/cell/fulltext/S0092-8674(20)31623-8
Hale, C. (2021, January 28). Mammoth Biosciences teams with Agilent to deliver CRISPR-based coronavirus tests. Retrieved from https://www.fiercebiotech.com/medtech/mammoth-biosciences-teams-agilent-to-deliver-crispr-based-coronavirus-tests
Hale, C. (2020, December 7). Pairing CRISPR with a smartphone camera, this COVID-19 test finds results in 30 minutes. Retrieved from https://www.fiercebiotech.com/medtech/pairing-crispr-a-smartphone-camera-covid-19-test-finds-results-30-minutes
Manke, K. (2021, January 7). 15-minute CRISPR-based COVID test uses smartphone camera to identify coronavirus. Retrieved from https://geneticliteracyproject.org/2021/01/07/15-minute-crispr-based-covid-test-uses-smartphone-camera-to-identify-coronavirus/
Soni, S. (2020, May 21). COVID-19 and gene editing: ethical and legal considerations. Retrieved from https://theconversation.com/covid-19-and-gene-editing-ethical-and-legal-considerations-138164
Vidyasagar, A. (2018, April 21). What is CRISPR? Retrieved from https://www.livescience.com/58790-crispr-explained.html
Article authors: Palak Agarwal, Sherilyn Wen
Article editor: Edie Whittington