---
OA_place: publisher
_id: '20737'
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "I also want to thank ISTA and the Austrian Science Fund FWF SFB
F78 (F7805) for financially\r\nsupporting my research."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
citation:
ama: Casado Polanco R. Role of NOTCH signaling in radial glial progenitor lineage
progression. 2025. doi:10.15479/AT-ISTA-20737
apa: Casado Polanco, R. (2025). Role of NOTCH signaling in radial glial progenitor
lineage progression. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20737
chicago: Casado Polanco, Raquel. “Role of NOTCH Signaling in Radial Glial Progenitor
Lineage Progression.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20737.
ieee: R. Casado Polanco, “Role of NOTCH signaling in radial glial progenitor lineage
progression,” Institute of Science and Technology Austria, 2025.
ista: Casado Polanco R. 2025. Role of NOTCH signaling in radial glial progenitor
lineage progression. Institute of Science and Technology Austria.
mla: Casado Polanco, Raquel. Role of NOTCH Signaling in Radial Glial Progenitor
Lineage Progression. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20737.
short: R. Casado Polanco, Role of NOTCH Signaling in Radial Glial Progenitor Lineage
Progression, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-12-09T09:04:18Z
date_published: 2025-12-09T00:00:00Z
date_updated: 2026-04-14T08:16:58Z
day: '09'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/AT-ISTA-20737
file:
- access_level: closed
checksum: 71e0fdf4619b0d70d03657ad7348137d
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: rcasadop
date_created: 2025-12-11T09:28:09Z
date_updated: 2025-12-11T11:18:37Z
file_id: '20793'
file_name: 2025_CasadoPolanco_Raquel_Thesis.docx
file_size: 78207207
relation: source_file
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checksum: 58cf2f25c33567723bc754a019c3e396
content_type: application/pdf
creator: rcasadop
date_created: 2025-12-11T09:28:04Z
date_updated: 2025-12-11T09:28:04Z
embargo: 2026-12-01
embargo_to: open_access
file_id: '20794'
file_name: 2025_CasadoPolanco_Raquel_Thesis.pdf
file_size: 6261874
relation: main_file
file_date_updated: 2025-12-11T11:18:37Z
has_accepted_license: '1'
keyword:
- NOTCH
- radial glial progenitor
- lineage progression
- cortical development
language:
- iso: eng
month: '12'
oa_version: Published Version
page: '133'
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication_identifier:
isbn:
- 978-3-99078-072-5
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Role of NOTCH signaling in radial glial progenitor lineage progression
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
corr_author: '1'
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2025-04-14T07:41:46Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...