mRNA therapeutics will fundamentally change the practice of Medicine.
Every once in a while, medicine changes in a fundamental way, and we may not realize it while it’s happening. I wasn’t around in 1928 when Fleming discovered penicillin, or in 1953 when Watson, Crick, and Franklin characterized the double-helical structure of DNA.
But looking at Medicine today, there are essentially two places where I think we will see, in retrospect, that we were at a fundamental turning point. One is artificial intelligence, which gets so much attention and hype that I will simply say yes, this will change things, stay tuned.
The other is a bit more obscure, but I suspect it may be just as impactful. That other thing is RNA therapeutics. The medicines of the future.
I want to start with the idea that many diseases are, fundamentally, a problem of proteins. In some cases, like hypercholesterolemia, the body is producing too much protein. In others, like hemophilia, too little.
When you think about disease this way, you realize that our current medications take effect late in the disease game. We have these molecules that try to block a protein from its receptor, or try to prevent a protein from cleaving another protein, or try to increase the rate that a protein is broken down. It’s all distal to the fundamental problem — the production of the bad protein in the first place.
Enter small inhibitory RNAs — siRNAs for short. Discovered in 1998 by Andrew Fire and Craig Mello at UMass Worcester, the two won the Nobel prize in medicine just 8 years later — that’s a really short time highlighting just how important this discovery was. Kariko and Weissman won the Nobel for mRNA vaccines this year, after inventing them 18 years ago, in contrast.
siRNAs are your bodies way of targeting proteins for destruction before they are ever created. About 20 base pairs long, siRNAs seek out a complementary target mRNA, attach to it, and call in a group of proteins to destroy it. With the target mRNA gone, no protein can be created.