Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus

Cortical organoids are 3D structures derived either from human embryonic stem cells or human induced pluripotent stem cells with their use exploding in recent years due to their ability to better recapitulate the human brain in vivo in respect to organization; differentiation; and polarity. Adeno-associated viruses (AAVs) have emerged in recent years as the vectors of choice for CNS-targeted gene therapy. Here; we compare the use of AAVs as a mode of gene expression in cortical organoids; over traditional methods such as lipofectamine and electroporation and demonstrate its ease-of-use in generating quick disease models through expression of different variants of the central gene-TDP-43-implicated in amyotrophic lateral sclerosis and frontotemporal dementia.

Automated summary

Cortical organoids derived from human stem cells are three-dimensional structures capable of better simulating the human brain. Adeno-associated viruses (AAVs) have emerged as a vector of choice for gene therapy targeting the central nervous system. In this study, AAVs were compared to traditional methods for gene expression in cortical organoids, and it was demonstrated that AAVs can easily generate disease models through the expression of different variants of the central gene TDP-43, implicated in neurodegenerative diseases.