Written by: Chris Shin '24
Edited by: Elaine Wang '24
Just decades ago, being able to change the genes that determine an organism’s identity was a pipe dream only seen in science fiction novels, but today, gene therapy might be the cornerstone of a treatment for the Coronavirus, responsible for infecting millions of people all over the world. On October 7, 2020, it was announced that Emmanuelle Charpentier and Jennifer A. Doudna would be awarded the Nobel Prize in Chemistry “for the development of a method for genome editing” . Though it was an incredible feat to for the pair of scientists to receive the greatest honor in the field of science, it came as no surprise; after all, they had developed a technique that allows scientists to become the master administrator of the genomes of organisms ranging from microscopic C. elegans, E. coli, and soon, humans.
This technique, named CRISPR, enables one to take a pair of biological “scissors” to cut and replace individual genes at will. The eventual goal of CRISPR is to be able to modify sequences of human DNA so that genetic diseases in patients can be prevented altogether .
At its essence, CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, is not a standalone procedure; they are genetic sequences first identified in microorganisms that exhibit two primary sections of DNA: sections of repeating nucleotides (the “Short Palindromic Repeats”), and sections that separate them apart (the “Regularly Interspaced”). The latter sections, called spacer DNA, were identified to contain remnants of DNA left by viruses that infected the microbes . After a microbe got infected by a virus, all future infections by the same virus did less harm to the microbe once the spacer DNA was incorporated, as if the bacteria had scanned the virus’s identity and prevented further invasions using this identification system .
When the virus attempts to replicate itself inside the territory of the bacteria, the spacer DNA is expressed as RNA, after which it binds to the virus’s genetic material. Once binded, they act as guide RNAs so that specialized enzymes called Cas (CRISPR associated) proteins can cut out the harmful nucleotide sequences which enable the virus to wreak havoc in the microorganism, now allowing one to replace such sequences with ones that can nullify the virus’s replicative ability .
The revolutionary aspect of the CRISPR technique is that much like a programmer editing their code quite literally at their fingertips, scientists can modify CRISPR sequences so that they can be used to cut out parts of other viruses that can cause harm to humans. For instance, it has been found that scientists could knock out HIV genomes in infected human T cells (white blood cells that circulate our bodies to induce immune responses ) simply by injecting gene vectors (molecules involved in the transport of external genetic material) containing guide RNAs with Cas9 proteins, one variant of Cas that can help target the deleterious genes of HIV, cutting them out so that they can be replaced with neutral genes . This example with HIV demonstrates the affordability, efficiency, and accessibility of CRISPR.
Another variant of Cas proteins known as Cas13 has recently been identified by researchers at Stanford and Duke to be able to target and dismantle the genetic sequences of SARS-COV-2, the virus responsible for the Coronavirus pandemic. The technique has a cute name, PAC-MAN (Prophylactic Antiviral CRISPR in human cells), and involves the binding of guide RNAs to the Coronavirus to facilitate the destruction of the virus and prevent it from reproducing , similarly to the HIV treatments described above.
So far, the only studies that have been conducted for treatments of both HIV and the Coronavirus have been done ex vivo, outside the human body. In addition, there are concerns that the injection of CRISPR genes could result in the targeting of too many human cells – even those unaffected by the virus – causing unnecessary harm to the entire body. Despite these concerns, the prospects are looking quite good in the world of CRISPR-related genetic engineering; it will only be a matter of time before CRISPR can be used to target cells within the human body to eliminate diseases that are plaguing the human population every single day.