April 15, 2024

Jessica A. Dennehy

10th Grade

Williamsville East High School

Genetic modification is the umbrella term indicating the process of altering the genetic makeup of an organism. Modifying the DNA of an organism can range from deleting segments, adding new segments, transferring segments from one organism to another, or even intentionally altering a singular base pair. Any organism that has been genetically modified would fall under the category of a genetically modified organism (GMO); they are typically used to improve a characteristic or trait, ranging from decreased susceptibility to disease to increased fertility. A variety of gene-editing technologies can be used in tandem or separately to genetically alter organisms; one of which is CRISPR/Cas-9.

CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, is a common gene-editing tool in the biology and medical field, originally taken from the DNA of bacteria. CRISPR, when in bacteria, was DNA fragments previously derived from destroyed bacteriophages or viruses that infected bacteria. These fragments were then integrated into the bacteria’s own DNA so that it would be able to easily recognize if the viral DNA was being reinjected into the cytosol. If so, CRISPR would proceed to be transcribed into RNA, which is then integrated into a “guide” for a Cas-9 protein. The Cas-9 protein would then cut up the viral DNA that CRISPR recognized, rendering it void and saving the bacteria from infection. Modern scientists have been able to substitute the RNA “guide” for any specific gene sequence for a desired gene of interest. This would allow them to alter and replace any particular DNA sequence with relative confidence that it and ONLY it has been altered. To further benefit, CRISPR is easily produced, widely attainable, and relatively inexpensive, allowing for mass applications of gene-editing technology for a variety of research purposes.

Yet how is this relevant to the recent ability to make swine anti-viral? Scientists have recently, through using CRISPR/Cas-9 technology, managed to disrupt a receptor on swine cells that porcine reproductive and respiratory syndrome (PRRS) utilized to infect the pigs. Without the CD163 receptor, PRRS has no possible way to initially infect swine cells, creating 100% immunity to the virus in ways that vaccines are simply unable to achieve. This application of CRISPR/Cas-9 in removing PRRS from the equation of the pork industry can save up to 2.7 billion dollars annually while also introducing the possibility of making swine anti-viral for other viruses, including but not limited to African Swine Fever Virus (ASFV), Porcine Epidemic Diarrhea Virus (PEDV), Pseudorabies Virus (PRV), Classical Swine Fever Virus (CSFV), and Transmissible Gastroenteritis Virus (TGEV). Furthermore, since CRISPR/Cas-9 was utilized to edit the pigs' genome by altering a singular sequence and not transferring DNA from a separate species, regulators of the process will treat the edited swine the same as the conventionally bred stock.

CRISPR/Cas-9, originally a bacterial adaptive immune response and system, has begun being integrated into human medicine and vaccines. Vaccines are used to introduce the immune system to a dead or weakened virus so that when a scenario involving a normal virus occurs, the body's immune system can “recognize” it via memory B cells and synthesize antibodies to combat the infection. Memory B cells are only possible if B cells were previously exposed to a particular virus, which is why there are so many different types of vaccines. However, modern medicine has discovered that  CRISPR/Cas-9 can bypass the lengthy process of memory B creation and directly engineer B cells to secrete specific antibodies by directly editing the genes to code for antibody synthesis. This would greatly benefit those who are immunocompromised and struggle to combat infections, as CRISPR/Cas-9 would essentially bypass the entirety of the process that has been affected, with the same, if not more efficient, end product of a working, normal immune system. From an educational standpoint, the usage of CRISPR/Cas-9 as a preventative viral precaution would also allow for further understanding of viral pathogenesis, gene therapy, and virus-host interactions.