Organoid transduction using recombinant adeno-associated viral vectors: Challenges and opportunities

Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno-associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it is associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors.