RNA interference, or RNAi, is the process by which long double-stranded RNA (ldsRNA) that codes for a unique protein in an organism is physically incorporated into the genome of said organism. The immune system of the organism recognizes the newly incorporated, ldsRNA as an allegedly harmful entity that must be eliminated from the body. The important thing here is that the immune system doesn’t distinguish between the RNA that the researcher has incorporated from the RNA that the body’s cells produce themselves, and reacts nonspecifically by destroying both forms of the RNA. Without any RNA, the messenger RNA transcript can’t be translated into a protein, and we see a “loss-of-function,” meaning the normal phenotype (observable trait) is not expressed. Essentially, a specific gene is silenced. For example, last semester in my intermediate genetics lab course, we used RNAi in the roundworm, Caenorhabditis elegans. By knocking down the “Rol-6” mutation in C. elegans using RNAi, my lab partner and I were able to cure the roundworms of their inherited Rol-6 mutation, which, untreated, caused spastic locomotion.
I’m researching the possibilities of using RNA interference as a way to treat chronic allergic reactions. Specifically, I’ve been focusing on the TSLP (thymic stromal lymphopoietin) protein, which is translated from the TSLP gene located on chromosome 5 in humans. The TSLP protein is responsible for maturation of T-cells through activation of antigen presenting cells (source: Reche PA, Soumelis V, Gorman DM, et al. (July 2001). “Human thymic stromal lymphopoietin preferentially stimulates myeloid cells”. J. Immunol. 167 (1): 336–43.). For this post, I won’t go into the details behind the biochemistry of allergic reactions, but I will say that my plan is to research the effects silencing or knocking-down the TSLP gene through RNAi, with the hope that this silencing or knock-down would prevent allergic reactions. My current biggest concern is whether the silencing of the TSLP gene would have negative side effects on the body, since the gene also functions in the maturation of myeloid dendritic cells (source: Reche PA, Soumelis V, Gorman DM, et al. (July 2001). “Human thymic stromal lymphopoietin preferentially stimulates myeloid cells”. J. Immunol. 167 (1): 336–43.). Stay tuned, more to come.