Benjamin Yurovsky | November 9, 2022

CRISPR, genome editing, genetic engineering. We often see these terms thrown around in the media or in everyday conversation. But what exactly is genetic editing and how does CRISPR fall into that category? Simply put, genome editing is active manipulation of a living organism’s genetic material via insertion, deletion or replacement of a DNA fragment. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) is the most developed and most popular approach to gene editing. 

CRISPR sequences were first detected in the E. coli genome in 1987 by Francisco Mojica, shortly prior to the massive outbreak of E. coli. Mojica, a scientist at the University of Alicante in Spain, hypothesized that CRISPRs were able to use remnants of genetic code from past invaders to detect and destroy future invaders. However it took until 2007 for Mojica’s prediction about CRISPR’s ability to safeguard against bacteriophages to be experimentally tested and proven. Leading to the 2007 breakthrough, scientists had deliberated the idea that CRISPR was being used by prokaryotes as a component in an adaptive immune system. Their hypothesis proved to be correct as the CRISPR Cas genes were able to store the makeup of attacking bacteriophages and destroy them upon resubjection.  

Oftentimes CRISPR technology is referred to as “CRISPR Cas-9.” This is because Cas-9 is the paramount enzyme produced by the CRISPR system. The Cas-9 enzyme functions by binding to the targeted DNA, cleaving it, and removing it from the code. The ability to silence specific genetic sequences allows researchers to better understand what each set of DNA codes for.

Although many other gene editing techniques exist, CRISPR is by far the most effective and promising. CRISPR Cas-9 is unique in that it does not need to be paired with a freestanding cleaving enzyme like so many other gene editing techniques. This editing tool can also be matched to RNA sequences that will eventually lead the Cas-9 to its desired DNA sequence. This is yet another unique feature that is possessed by the revolutionary system.

Although CRISPR is most notable for its ability to assist with determining functionality of certain genes, it has a couple more uses. Over the course of the last few years, CRISPR has developed into a tool that assists researchers in creating replicates and models. With the use of these animal and cell models, scientists are able to increase the speed in which they examine and analyze diseases such as cancer and mental illness. 
Even within our own facilities, we are making massive strides in the medical industry with the help of CRISPR technology. In Ian Macara’s lab, a graduate student named Maria Fomicheva has been able to discover a “genetic switch” that significantly contributes to continuous cell division – a marker of cancer. The researchers in the Macara Lab research cells that specifically had lost the ability to divide upon obtaining a specific, high density. They had screened about 40 million cells and were able to identify NF2: a tumor suppressor that indicated that the researchers were on track with their experiment. However, upon the removal of the TRAF3 protein, the cell’s signaling ability was blocked. This was the first time that the TRAF3 protein was thought to be linked to density-dependent proliferation. The newly discovered link between TRAF3 and cancer makes it an incredibly interesting and important topic to explore.

Bibliography

CRISPR history and development for Genome Engineering. Addgene. (n.d.). Retrieved October 25, 2022, from https://www.addgene.org/crispr/history/ 

Questions and answers about CRISPR. Broad Institute. (2018, August 4). Retrieved October 25, 2022, from https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr 

Shapiro, M. (1970, March 10). NEW CRISPR screening technique developed at Vanderbilt leads to discovery of pathway that may be linked to cancer initiation. Vanderbilt University. Retrieved October 25, 2022, from https://news.vanderbilt.edu/2021/03/10/a-new-crispr-screening-technique-developed-at-vanderbilt-leads-to-the-discovery-of-a-pathway-that-may-be-linked-to-cancer-initiation/ U.S. National Library of Medicine. (n.d.). What are genome editing and CRISPR-Cas9?: Medlineplus Genetics. MedlinePlus. Retrieved October 25, 2022, from https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/