RNAi: Another Reason to Cheer for Basic Research

We recently talked about how Green Fluorescent Protein, restriction enzymes, and CRISPR are invaluable products of basic research. These investigations did not specifically go after a particular human ailment or disease, but were more directed towards enhancing our understanding of the world. These examples are just a few of the famous outcomes of basic research, and we cannot refrain from talking about just one more, RNA interference (RNAi).

RNAi research had an unlikely start through the study of petunias and not through typical medical research. Petunias are known for their bright, beautiful colors. Scientists wanted to make these flowers even more intensely colorful by carrying out what seemed to be a straightforward approach: insert the gene that is responsible for the pigmentation. However, the results were not as straightforward as initially predicted. In some cases, the petunias actually lost their color and turned white.¹ Apparently, the genes were working against each other, rather than combining their strengths.

Many answers were found working with the humble roundworm Caenorhabditis elegans. Nobel Prize winners Andrew Fire and Craig Mello directed research in which RNA was injected into the worm.² When sense RNA (a molecule identical to a stretch of messenger RNA) was injected, no obvious effects were observed. Again, nothing happened upon injecting antisense RNA (the RNA whose base pairs complement those of the sense RNA). But when both a strand of sense and antisense RNA were injected, the target protein of that particular mRNA was substantially reduced. Through their hard work, scientists had thus come across a biological process now known as RNA interference. Double-stranded RNA is used by cellular machinery to track down specific stretches of messenger RNA and break it down. No protein is formed, so the gene is essentially put on “mute.”

Because of the specificity in targeting a gene of interest, RNAi has been used extensively in drug discovery. In fact, one of the ways RNAi is used in drug discovery is through RNAi pathway analysis. Turning off a gene via RNAi often helps researchers validate a drug target. Additionally, much hope has also been placed into using RNAi as a treatment of its own. However, significant challenges, such as transporting the RNA molecules into cells, put a damper on initial enthusiasm, but optimism is rising again that RNAi drugs will make it to the market.

But where would RNAi be today if all financial support was directed to “sure bets” and “obvious applicability?” So much innovation in the drug discovery world has been gained by treading into the vast, uncharted territory known as basic research, and there is still plenty to discover. Let’s explore!