简单说明
Cells have a built-in system for shredding RNA messages they recognise as unwanted. RNA interference feeds that system a short piece of RNA matching the gene you want quietened, and the cell destroys those messages for you. It is temporary — repeat dosing is required — and it is not gene editing at all, but it is the closest comparison for many of the same diseases, and it has approved medicines.
深入了解
Small interfering RNAs are loaded into the RNA-induced silencing complex, where the guide strand directs Argonaute-mediated cleavage of complementary mRNA. GalNAc conjugation gives efficient hepatocyte uptake, making the liver the dominant target tissue. Approved siRNA medicines exist for several conditions, including hereditary transthyretin amyloidosis — where they compete directly with in vivo CRISPR programmes aimed at the same gene.
The honest comparison with gene editing
For ATTR amyloidosis, the same target gene — TTR — is addressed by approved RNAi medicines given repeatedly and by an investigational one-time CRISPR knockout. The editing approach offers a single administration; the RNAi approach offers years of accumulated safety data and the ability to stop. Neither answer is obviously right, and it is the clearest example on this site of why 'newer' does not settle a clinical question.
Sources
- Nature (Fire et al.) · 1998
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans ↗