Don't fear the CRISPR†
Derek Lowe
First published on 21st October 2016
Abstract
Does simple gene-editing mean the end of traditional medicinal chemistry? Probably not.
CRISPR! Yet another article about CRISPR! Can you stand it? So much has been written about this gene-editing technique already that you'd think it had been discovered through grants from the publishing industry. But I'd like to look at its potential impact on medicinal chemistry.
The first thing that many medicinal chemists might think is that they've seen this show before. In the late 1980s and early 1990s, it was going to be antisense that ‘changed everything’, and more recently it's been RNA-directed therapies. A jaded chemist could be forgiven for thinking that CRISPR is more of the same: an interesting biological technique surfing towards the clinic on a foaming, breaking wave of hype. A look at the remains from some of the earlier surges – out there bleaching on the rocks, in tatters – does not inspire enthusiasm.
This one could well be different, although I realise those words have been uttered before. Still, CRISPR is surely the easiest and most versatile gene-editing platform yet discovered, and that certainly counts for a lot. For medicinal chemists, at the very least it means a variety of new cell and whole-organism models of disease, along with new ways to help untangle mechanisms of action (or, inevitably, to tangle up some of the ones we thought we already understood).
As for clinical applications, these seem to be coming on faster than for any other such technique. It looks likely the first human trials for the technology will be in further engineering chimeric antigen receptor T-cells (CAR-T) in cancer immunotherapy, which is a natural experiment to try, given the wide belief that removing some functions from those cells should make them more effective at their new tasks. A trial in China should be underway by the time you read this, and one in the US is slated to start by the end of the year.
Derek Lowe (@Dereklowe) is a medicinal chemist working on preclinical drug discovery in the US. He blogs at http://blogs.sciencemag.org/pipeline/.
Footnote |
| † This article was originally published in Chemistry World, first published online on 31 August 2016. |
| This journal is © The Royal Society of Chemistry 2016 |