Welcome to Impact RNA Factor, your weekly commentary on the latest medical research. I’m Dr. F. Perry Wilson from the Yale School of Medicine.
In the evolution of medicine, there are pivotal moments that reshape our understanding. I wasn’t present when Fleming discovered penicillin in 1928 or when Watson, Crick, and Franklin unraveled the DNA double helix in 1953.
RNA
Today, two transformative shifts seem apparent, one being the well-discussed field of artificial intelligence, promising substantial changes. The second, although less conspicuous, carries equal weight: RNA therapeutics, a harbinger of future medicines.
Consider the premise that many diseases fundamentally stem from protein dysregulation. Conditions like hypercholesterolemia involve excessive protein production, while others, like hemophilia, result from insufficient production.
Existing medications often intervene downstream in the disease process. These molecules aim to block receptor interactions, inhibit protein cleavage, or accelerate protein degradation—actions occurring distal to the root issue: the synthesis of the problematic protein.
Enter small inhibitory RNAs (siRNAs), unveiled in 1998 by Andrew Fire and Craig Mello at UMass Worcester, garnering a Nobel Prize just eight years later. In contrast, Nobel laureates Karikó and Weissman received recognition for mRNA vaccines 18 years after their invention.
siRNAs represent the body’s preemptive strike against unwanted proteins. These approximately 20-base pair molecules selectively target complementary mRNA, binding and recruiting a set of proteins to annihilate it. Without the target mRNA, the protein synthesis process is halted.
Consider the implications: How does high cholesterol pose a threat? Proteins. How does Staphylococcus aureus prove fatal? Proteins. Even viruses rely on RNA-to-protein conversion for replication.
The spotlight on siRNAs intensifies with a recent JAMA paper outlining a compelling application. Elevated lipoprotein(a), akin to LDL, correlates with cardiovascular disease, heart attacks, and strokes. Yet, statins and dietary adjustments show minimal impact on lipoprotein(a) levels, suggesting a strong genetic influence.
The promise of siRNAs lies in their ability to target and neutralize these genetic factors, paving the way for a new frontier in medical therapeutics. As we navigate these transformative times, the impact of RNA therapeutics on disease intervention cannot be overstated. Stay tuned for the unfolding narrative of medical progress.
