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@ARTICLE{Hartley:290486,
author = {A. Hartley$^*$ and L. Burger$^*$ and C. Wincek$^*$ and L.
Dons and T. Li and A. Grewenig$^*$ and T. Taşgın$^*$ and
M. Urban$^*$ and A. Roig-Merino$^*$ and M. Ghazvini and R.
Harbottle$^*$},
title = {{A} {S}imple {N}onviral {M}ethod to {G}enerate {H}uman
{I}nduced {P}luripotent {S}tem {C}ells {U}sing {SMAR} {DNA}
{V}ectors.},
journal = {Genes},
volume = {15},
number = {5},
issn = {2073-4425},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2024-01113},
pages = {575},
year = {2024},
note = {#EA:D420#LA:D420#},
abstract = {Induced pluripotent stem cells (iPSCs) are a powerful tool
for biomedical research, but their production presents
challenges and safety concerns. Yamanaka and Takahashi
revolutionised the field by demonstrating that somatic cells
could be reprogrammed into pluripotent cells by
overexpressing four key factors for a sufficient time. iPSCs
are typically generated using viruses or virus-based
methods, which have drawbacks such as vector persistence,
risk of insertional mutagenesis, and oncogenesis. The
application of less harmful nonviral vectors is limited as
conventional plasmids cannot deliver the levels or duration
of the factors necessary from a single transfection. Hence,
plasmids that are most often used for reprogramming employ
the potentially oncogenic Epstein-Barr nuclear antigen 1
(EBNA-1) system to ensure adequate levels and persistence of
expression. In this study, we explored the use of nonviral
SMAR DNA vectors to reprogram human fibroblasts into iPSCs.
We show for the first time that iPSCs can be generated using
nonviral plasmids without the use of EBNA-1 and that these
DNA vectors can provide sufficient expression to induce
pluripotency. We describe an optimised reprogramming
protocol using these vectors that can produce high-quality
iPSCs with comparable pluripotency and cellular function to
those generated with viruses or EBNA-1 vectors.},
keywords = {Induced Pluripotent Stem Cells: cytology / Induced
Pluripotent Stem Cells: metabolism / Humans / Genetic
Vectors: genetics / Cellular Reprogramming: genetics /
Fibroblasts: cytology / Fibroblasts: metabolism / Plasmids:
genetics / Epstein-Barr Virus Nuclear Antigens: genetics /
Cells, Cultured / Transfection: methods / S/MAR (Other) /
SMAR DNA vector (Other) / iPSC (Other) / nonviral (Other) /
reprogramming (Other) / stem cells (Other) / Epstein-Barr
Virus Nuclear Antigens (NLM Chemicals) / EBV-encoded nuclear
antigen 1 (NLM Chemicals)},
cin = {D420},
ddc = {570},
cid = {I:(DE-He78)D420-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38790204},
pmc = {pmc:PMC11121542},
doi = {10.3390/genes15050575},
url = {https://inrepo02.dkfz.de/record/290486},
}