RNAi Therapeutics How Likely, How Soon 英文参考文献.docVIP

Feature RNAi Therapeutics: How Likely, How Soon? Richard Robinson R NA interference (RNAi) has been called “one of the most exciting discoveries in biology in the last couple decades,” and since it was ?rst recognized by Andrew Fire et al. in 1998, it has quickly become one of the most powerful and indispensable tools in the molecular biologist’s DOI: 10.1371/journal.pbio.0020028.g001 toolkit. Using short double-stranded RNA (dsRNA) molecules, RNAi Figure 1. Ribozymes A ribozyme binds to a speci?c mRNA, cleaves it, and thus prevents it from functioning. can selectively silence essentially any gene in the genome. It is an ancient mechanism of gene regulation, found in eukaryotes as diverse as yeast and mammals, and probably plays a central role in controlling gene expression in all eukaryotes. In the lab, RNAi is routinely used to reveal the genetic secrets of development, intracellular signaling, cancer, infection, and a full range of other phenomena. But can the phenomenon hailed by the journal Science as the “Breakthrough of the Year” in 2002 break out of the lab and lead to novel therapies as well? Pharmaceutical giants are hoping so, and several biotech companies have bet their futures on it, but not everyone is sanguine about the future of RNAi therapy. Clinical Na?veté, Mysterious Mechanisms have the characteristics to be a drug,” he says. No ribozyme has yet been approved for use by the United States Food and Drug Administration (FDA). Similarly, despite much initial To be a successful drug, a molecule must overcome a long set of hurdles. First, it must be able to be manufactured at reasonable cost and administered safely and conveniently. Then, and even more importantly, it must be stable enough to reach its target cells before it is degraded or excreted; it must get into those cells, link up with its intracellular target, and exert its effect; and it must exert enough of an effect to improve the health of the person taking it. And, ?nally, it must do all