Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain

Josse A. Depla; Marina Sogorb-Gonzalez; Lance A. Mulder; Vivi M. Heine; Pavlina Konstantinova; Sander J. van Deventer; Katja C. Wolthers; Dasja Pajkrt; Adithya Sridhar; Melvin M. Evers

doi:10.1016/j.omtm.2020.05.028

Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain

Josse A. Depla
, Marina Sogorb-Gonzalez
, Lance A. Mulder
, Vivi M. Heine
, Pavlina Konstantinova
, Sander J. van Deventer
, Katja C. Wolthers
, Dasja Pajkrt
, Adithya Sridhar
, Melvin M. Evers^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Induced pluripotent stem cell-derived cerebral organoids are an innovative human model of the brain that could improve translation of gene therapy to the clinic. Depla et al. demonstrate the application of cerebral organoids as a preclinical model for AAV capsid selection and testing efficacy of therapeutic transgenes.

Original language	English
Pages (from-to)	167-175
Number of pages	9
Journal	Molecular Therapy - Methods and Clinical Development
Volume	18
Early online date	1 Jun 2020
DOIs	https://doi.org/10.1016/j.omtm.2020.05.028
Publication status	Published - 11 Sept 2020

Funding

We thank Fanny Martier, Cynthia Brouwers, and Sonay Keskin for helping with the qPCR and TR-FRET experiments, and Bas Bosma, Francois Du Plessis, and Jacek Lubelski for providing the AAVs. We thank Lukas Schwarz, Sumiati Baatjes, and Valerie Sier-Ferreira for input and assisting with staining and imaging of the cerebral organoids; Ron Hoeben and Daisy Picavet for helping with the analysis of the confocal images; Ellen Broug and Sietske Gadella for critical reading of the manuscript; and all group members for helpful discussions. This research received funding by European Union's Horizon 2020 innovative training network under grant number 812673 (OrganoVIR). We thank Fanny Martier, Cynthia Brouwers, and Sonay Keskin for helping with the qPCR and TR-FRET experiments, and Bas Bosma, Francois Du Plessis, and Jacek Lubelski for providing the AAVs. We thank Lukas Schwarz, Sumiati Baatjes, and Valerie Sier-Ferreira for input and assisting with staining and imaging of the cerebral organoids; Ron Hoeben and Daisy Picavet for helping with the analysis of the confocal images; Ellen Broug and Sietske Gadella for critical reading of the manuscript; and all group members for helpful discussions. This research received funding by European Union’s Horizon 2020 innovative training network under grant number 812673 (OrganoVIR).

Funders	Funder number
European Union's Horizon 2020 innovative training network
European Union’s Horizon 2020 innovative training network
Lukas Schwarz
Horizon 2020 Framework Programme	812673

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

AAV
adeno-associated virus
central nervous system
Cerebral organoids
CNS
gene therapy
induced pluripotent stem cells
iPSC
micro RNA
miRNA
organoids
SCA3
spinocerebellar ataxia 3
Transduction

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Depla, J. A., Sogorb-Gonzalez, M., Mulder, L. A., Heine, V. M., Konstantinova, P., van Deventer, S. J., Wolthers, K. C., Pajkrt, D., Sridhar, A., & Evers, M. M. (2020). Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain. Molecular Therapy - Methods and Clinical Development, 18, 167-175. https://doi.org/10.1016/j.omtm.2020.05.028

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title = "Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain",

abstract = "Induced pluripotent stem cell-derived cerebral organoids are an innovative human model of the brain that could improve translation of gene therapy to the clinic. Depla et al. demonstrate the application of cerebral organoids as a preclinical model for AAV capsid selection and testing efficacy of therapeutic transgenes.",

keywords = "AAV, adeno-associated virus, central nervous system, Cerebral organoids, CNS, gene therapy, induced pluripotent stem cells, iPSC, micro RNA, miRNA, organoids, SCA3, spinocerebellar ataxia 3, Transduction",

author = "Depla, \{Josse A.\} and Marina Sogorb-Gonzalez and Mulder, \{Lance A.\} and Heine, \{Vivi M.\} and Pavlina Konstantinova and \{van Deventer\}, \{Sander J.\} and Wolthers, \{Katja C.\} and Dasja Pajkrt and Adithya Sridhar and Evers, \{Melvin M.\}",

year = "2020",

month = sep,

day = "11",

doi = "10.1016/j.omtm.2020.05.028",

language = "English",

volume = "18",

pages = "167--175",

journal = "Molecular Therapy - Methods and Clinical Development",

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Depla, JA, Sogorb-Gonzalez, M, Mulder, LA, Heine, VM, Konstantinova, P, van Deventer, SJ, Wolthers, KC, Pajkrt, D, Sridhar, A & Evers, MM 2020, 'Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain', Molecular Therapy - Methods and Clinical Development, vol. 18, pp. 167-175. https://doi.org/10.1016/j.omtm.2020.05.028

TY - JOUR

T1 - Cerebral Organoids

T2 - A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain

AU - Depla, Josse A.

AU - Sogorb-Gonzalez, Marina

AU - Mulder, Lance A.

AU - Heine, Vivi M.

AU - Konstantinova, Pavlina

AU - van Deventer, Sander J.

AU - Wolthers, Katja C.

AU - Pajkrt, Dasja

AU - Sridhar, Adithya

AU - Evers, Melvin M.

PY - 2020/9/11

Y1 - 2020/9/11

N2 - Induced pluripotent stem cell-derived cerebral organoids are an innovative human model of the brain that could improve translation of gene therapy to the clinic. Depla et al. demonstrate the application of cerebral organoids as a preclinical model for AAV capsid selection and testing efficacy of therapeutic transgenes.

AB - Induced pluripotent stem cell-derived cerebral organoids are an innovative human model of the brain that could improve translation of gene therapy to the clinic. Depla et al. demonstrate the application of cerebral organoids as a preclinical model for AAV capsid selection and testing efficacy of therapeutic transgenes.

KW - AAV

KW - adeno-associated virus

KW - central nervous system

KW - Cerebral organoids

KW - CNS

KW - gene therapy

KW - induced pluripotent stem cells

KW - iPSC

KW - micro RNA

KW - miRNA

KW - organoids

KW - SCA3

KW - spinocerebellar ataxia 3

KW - Transduction

UR - https://www.scopus.com/pages/publications/85086864813

UR - https://www.scopus.com/pages/publications/85086864813#tab=citedBy

U2 - 10.1016/j.omtm.2020.05.028

DO - 10.1016/j.omtm.2020.05.028

M3 - Article

AN - SCOPUS:85086864813

SN - 2329-0501

VL - 18

SP - 167

EP - 175

JO - Molecular Therapy - Methods and Clinical Development

JF - Molecular Therapy - Methods and Clinical Development

ER -

Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain

Abstract

Funding

UN SDGs

Keywords

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