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@ARTICLE{Zhang:1044403,
author = {Zhang, Jiao and Bing, Ziyu and Marie, Corinne and Izsvák,
Zsuzsanna and Müller, Frank and Thumann, Gabriele and
Walter, Peter and Johnen, Sandra},
title = {{E}ffect of degeneration stage on non-viral tissue
transfection of rd10 retina ex vivo},
journal = {Molecular therapy / Nucleic Acids},
volume = {36},
number = {3},
issn = {2162-2531},
address = {New York, NY},
publisher = {Nature Publ. Group},
reportid = {FZJ-2025-03167},
pages = {102616 -},
year = {2025},
note = {This work was supported by the Confocal Microscope Facility
and the Immunohistochemistry Facility, core facilities of
the Interdisciplinary Center for Clinical Research (IZKF)
Aachen within the Faculty of Medicine at RWTH Aachen
University. Thethors thank Anne Freialdenhoven, Antje
Schiefer, and Alicia Hühnlein (Department of Ophthalmology,
University Hospital RWTH Aachen) for excellent
technicaltance. This work was funded by the China
Scholarship Council (no. 202208080251) and is part of a
graduate school funded by the Deutsche
Forschungsgemeinschaft DFG under GRK 2610/01. The results
shown here are part of the doctoral thesis of J.Z.},
abstract = {Gene therapy has great potential for the treatment of
inherited retinal diseases, as evidenced by the progress and
ongoing research. Using the Sleeping Beauty (SB) transposon
system, we developed a non-viral gene delivery system for
electroporation-based transfection of rd10 retinas ex vivo.
SB100X transposase and Venus transposon plasmids were
transfected at a ratio of 1:16 into rd10 retinas of
different ages and corresponding wild-type (WT) controls.
Transfection efficiency was assessed by fluorescence
microscopy and transfected cells were identified by
immunohistochemistry. Retinal integrity and cell viability
were assessed by FITC-dextran electroporation, histology,
and apoptosis assay. The highest transfection efficiency was
observed in degenerated stages P61 and older, with Müller
cells being the only transfected cell type. A $31\%$
reduction in transposon plasmid size resulted in a 1.5-fold
increase in transfection efficiency. Integrity and
morphology of degenerated retinas were preserved after
electroporation-based plasmid transfer; the number of
apoptotic cells in the inner nuclear layer (INL) was reduced
by half compared to WT controls. We demonstrated that
electroporation-based delivery of the SB transposon system
resulted in efficient transfection of degenerated retinas.
Our results are an important first step toward the combined
use of retinal prostheses and gene therapy to improve the
treatment of inherited retinal dystrophies.},
cin = {IBI-1 / INW-1},
ddc = {610},
cid = {I:(DE-Juel1)IBI-1-20200312 / I:(DE-Juel1)INW-1-20231219},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524) / GRK 2610 - GRK 2610: Innovative Schnittstellen
zur Retina für optimiertes künstliches Sehen -
InnoRetVision (424556709)},
pid = {G:(DE-HGF)POF4-5244 / G:(GEPRIS)424556709},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.omtn.2025.102616},
url = {https://juser.fz-juelich.de/record/1044403},
}