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

Ann-Na Cho; Fiona Bright; Nicolle Morey; Carol Au; Lars M Ittner; Yazi D Ke

doi:10.3390/cells11203194

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

Cells. 2022 Oct 11;11(20):3194. doi: 10.3390/cells11203194.

Authors

Ann-Na Cho¹, Fiona Bright¹, Nicolle Morey¹, Carol Au¹, Lars M Ittner¹, Yazi D Ke¹

Affiliation

¹ Dementia Research Centre, Macquarie Medical School, Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia.

Abstract

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.

Keywords: Adeno-associated viruses (AAVs); TDP-43; cortical organoids; gene delivery; neurodegenerative disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA-Binding Proteins / metabolism
Dependovirus / genetics
Gene Expression
Humans
Induced Pluripotent Stem Cells* / metabolism
Organoids* / metabolism
Stem Cells

Substances

DNA-Binding Proteins

Grants and funding

This research was funded by National Health and Medical Research Council: #1123564, #1132524, #1136241, #1143848, #2001572; Australian Research Council: #DP170100781, #DP210101957; MND Research Australia: Betty and John Laidlaw MND Research Prize 2021;Macquarie University: MQRF 2020-2022.