2026-06-14T03:28:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65492024-11-29T18:12:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Senís, Elena
author
Mosteiro, Lluc
author
Wilkening, Stefan
author
Wiedtke, Ellen
author
Nowrouzi, Ali
author
Afzal, Saira
author
Fronza, Raffaele
author
Landerer, Henrik
author
Niopek, Dominik
author
Schmidt, Manfred
author
Serrano Marugan , Manuel
author
Grimm, Dirk
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Heidelberg University (Alemania)
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2018-10-29T10:28:05Z
2018-10-29T10:28:05Z
2018-07-09
Nat Commun. 2018; 9(1): 2651.
10.1038/s41467-018-05059-x
2041-1723
2041-1723
Nature communications
29985406
http://hdl.handle.net/20.500.12105/6549
In vivo reprogramming of somatic cells into induced pluripotent stem cells (iPSC) holds vast potential for basic research and regenerative medicine. However, it remains hampered by a need for vectors to express reprogramming factors (Oct-3/4, Klf4, Sox2, c-Myc; OKSM) in selected organs. Here, we report OKSM delivery vectors based on pseudotyped Adeno-associated virus (AAV). Using the AAV-DJ capsid, we could robustly reprogram mouse embryonic fibroblasts with low vector doses. Swapping to AAV8 permitted to efficiently reprogram somatic cells in adult mice by intravenous vector delivery, evidenced by hepatic or extra-hepatic teratomas and iPSC in the blood. Notably, we accomplished full in vivo reprogramming without c-Myc. Most iPSC generated in vitro or in vivo showed transcriptionally silent, intronic or intergenic vector integration, likely reflecting the increased host genome accessibility during reprogramming. Our approach crucially advances in vivo reprogramming technology, and concurrently facilitates investigations into the mechanisms and consequences of AAV persistence.
eng
STEM-CELLS
GENE-TRANSFER
MOUSE-LIVER
CLINICAL TRANSLATION
EFFICIENT TRANSDUCTION
HUMAN FIBROBLASTS
AAV INTEGRATION
SKELETAL-MUSCLE
VECTORS
EXPRESSION
AAVvector-mediated in vivo reprogramming into pluripotency
journal article
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