CRISPR-CaS: How Bacteria Held the Key in Modern Genetic Editing

Upon first reviewing the lectures for the upcoming week, I saw the word CRISPR-CaS and I honestly did not have a single clue as to what it meant. After a quick internet search, it turns out that this funny-looking word is actually the forefront of modern DNA editing. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a key component of bacterial immunity from invaders such as bacteriophages. The bacterial CRISPR-CaS system contains two parts: first there is CRISPR-associated nuclease (CaS) which acts as molecular "scissors" that cuts and binds target DNA sequences. Then, there is a guide RNA sequence (gRNA) which acts as a sort of GPS and directs the CaS nuclease to its target DNA sequence.

In order to fully understand CRISPR's role in human genetic editing, it is important to understand how bacteria utilize CRISPR-CaS in order to fend off predators. First, a bacteria needs an invader that is attempting to attach onto the bacterium, this bacterial prey then CaS nuclease to cut a piece of viral DNA from the invader known as a protospacer. (Synthego, 2022) This fragment of DNA is stored by the bacterium as a sort of immune memory in a palindromic sequence, so that next time the same viral DNA tries to attack, the bacterium can use CaS9 which cuts the viral DNA therefore debilitating the invader. The key factor here is the gRNA, which, as I mentioned earlier, acts as a sort of guide that moves CRISPR-associated nuclease towards the target DNA. The gRNA is what two marvelous women in STEM (yay!) Dr. Jennfier Doudna and Dr. Emmanuel Charpentier questioned to be manipulated in order for scientists to be able to direct this CaS nuclease to cut anywhere in the DNA sequence that they wanted. Therefore, once modern genetic scientists learned how to properly manipulate gRNA, they were able to cut anywhere in a DNA sequence that they desired, which then opens the possibility of inserting new strands of DNA in this space - this is where CRISPR-CaS' role in modern medicine takes place.

For decades, my family has been plagued by Huntington's Disease, which is an extremely fatal genetic disease caused by a defective gene on chromosome 4. Huntington's is a disease that does not have a cure and is known to be a death sentence upon diagnosis. Huntington's results in the complete destruction of one's cognitive and muscular abilities thus rendering them completely unable to walk, talk, eat, and even think. It is a 50% chance of getting the disease if a parent has it, thankfully, my grandmother was a part of the 50% to not get the disease, however, having to witness some of our loved ones going from normal 30-40 year-olds to being unable to even walk or talk has been hard on my family. Due to the genetic foundation of the disease, as of 2021, CRISPR technologies are currently being tested on mice with a defective huntingtin gene and has shown promising results in the search for a cure. Using CRISPR, the huntingtin mutation is simply cut out of the genome sequence on chromosome 4, and a normal sequence is then placed. This treatment has been seen to have significantly lowered the levels of neuronal degeneration as well has lowered the cerebellar arteriolar blood volume, which is a key symptom of early onset Huntington's symptoms. (Duan, 2021)

Although CRISPR-CaS has been uplifted as a prominent factor in modern DNA editing, there has been question regarding the morality of it. CRISPR holds a lot of power that can render humans immune to various diseases and/or genetic abnormalities. Recently within pop culture, the term "designer babies" has come to light after certain celebrities have spoken out about wanting to pick and choose certain aspects of their child that they want, such as hair color, melanin levels, eye color, immunity to possible familial diseases, and even going so far to edit height. Kim Kardashian has been known to have picked her children's genders before conception and even going so far to make sure they do not end up with the same auto-immune disorder that she has that lead to her severe psoriasis diagnosis. Moreover, the utter price of CRISPR is astonishing which may encourage a larger gap between the upper and lower classes that could be seen along the line through healthier, more genetically-apt offspring of the upper class as a result of the accessibility of CRISPR.