35 — AAV-mediated CRISPR/Cas gene editing of retinal cells in vivo

CRISPR/Cas9 therapy has enormous (enormous, I say!) implications for the future of medicine. But you already knew that, didn’t you?

In this study, the authors use adeno-associated virus 2 (AAV2) to modify retina cells of a living mouse. In particular, this mouse is a Thy1-YFP transgenic mouse, which means that certain retinal cells (RGCs, amacrine, and bipolar) can be induced to fluoresce yellow. The mice were then anesthetized and injected with the AAV2 vector designed to eliminate the YFP qualities of the cells.

The experiment was designed this way to demonstrate the feasibility of an in vivo therapy: Because the fluorescence can be detected without killing the mice, it’s a good model for the utility of this method for clinical gene-therapy in humans.

The results: The study demonstrates a ~80% reduction in YFP-positive cells, with no substantial difference in retinal function (especially considering a retinal injection in mouse-eyes is, I imagine, a pretty large needle-to-eye-size ratio). So that’s good.

This means that this is a feasible model for human ophthalmic disease therapies, plus or minus a few years and tens of millions of dollars of research.