Human stem cell-based retina on chip as new translational model for validation of AAV retinal gene therapy vectors

Gene therapies using adeno-associated viruses (AAVs) are among the most promising strategies to treat or even cure hereditary and acquired retinal diseases. However, the development of new efficient AAV vectors is slow and costly, largely because of the lack of suitable non-clinical models. By faithfully recreating structure and function of human tissues, human induced pluripotent stem cell (iPSC)derived retinal organoids could become an essential part of the test cascade addressing translational aspects. Organ-on-chip (OoC) technology further provides the capability to recapitulate microphysiological tissue environments as well as a precise control over structural and temporal parameters. By employing our recently developed retina on chip that merges organoid and OoC technology, we analyzed the efficacy, kinetics, and cell tropism of seven first- and second-generation AAV vectors. The presented data demonstrate the potential of iPSC-based OoC models as the next generation of screening platforms for future gene therapeutic studies.

Automated summary

Gene therapies using AAVs show promise in treating or curing retinal diseases, but the development of efficient AAV vectors is slow and costly due to the lack of suitable non-clinical models. Human iPSC-derived retinal organoids faithfully recreate human tissue structure and function, making them essential for translational research. OoC technology allows for the recapitulation of tissue environments and precise control over parameters, with iPSC-based OoC models showing potential as the next generation of screening platforms for gene therapeutic studies.