Magnetically Guided Adeno-Associated Virus Delivery for the Spatially Targeted Transduction of Retina in Eyes.

Adeno-associated viruses (AAVs) are intensively explored for gene therapies in general and have found promising applications for treating retina diseases. However, controlling the specificity (tropism) and delivery of AAVs to selected layers, cell types, and areas of the retina is a major challenge to further develop retinal gene therapies. Magnetic nanoparticles (MNPs) provide effective delivery platforms to magnetically guide therapeutics to target cells. Yet, how MNPs can deliver AAVs to transfect particular retina layers and cells remains elusive. Here, it is demonstrated that MNPs can be used to transport different AAVs through the retina and to modulate the selective transduction of specific retinal layers or photoreceptor cells in ex vivo porcine explants and whole eyes. Thereby, transduction is triggered by bringing the viruses in close proximity to the target cell layer and by controlling their interaction time. It is shown that this magnetically guided approach to transport AAVs to selected areas and layers of the retina does not require the cell-specific optimization of the AAV tropism. It is anticipated that the new approach to control the delivery of AAVs and to selectively transduce cellular systems can be applied to many other tissues or organs to selectively deliver genes of interest.