Delivery of Antisense Oligonucleotides to the Mouse Retina.

The eye is the organ in charge of vision and, given its properties, has become an excellent organ to test genetic therapies, including antisense oligonucleotide (AON) technology. In fact, the first AON receiving FDA and EMA approval was meant to treat an eye condition. Currently, dozens of clinical trials are being conducted for a variety of subtypes of inherited retinal disease. Although most of them are based on gene augmentation therapies, a phase 3 and two phase 1/2 clinical trials using AONs are ongoing. Since the retina is a layered structure of nondividing cells, obtaining human retinal tissue and expanding it in the lab is not possible, unless induced pluripotent stem cell technology is used. Mouse models have helped to elucidate the function of many genes, and the retinal structure is quite similar to that of humans. Thus, drug delivery to the mouse eye can provide valuable information for further optimization of therapies. In this chapter, the protocol for intravitreal injections of AONs is described in detail.