Format

Send to

Choose Destination
Nat Commun. 2018 Jul 9;9(1):2651. doi: 10.1038/s41467-018-05059-x.

AAVvector-mediated in vivo reprogramming into pluripotency.

Author information

1
Virus-Host Interaction Group, Department of Infectious Diseases/Virology, Heidelberg University Hospital, Cluster of Excellence CellNetworks, Heidelberg, 69120, Germany.
2
BioQuant, University of Heidelberg, Heidelberg, 69120, Germany.
3
Cellular Plasticity and Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, 08035, Spain.
4
Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain.
5
Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
6
GeneWerk GmbH, Heidelberg, 69120, Germany.
7
Institute for Pharmacy and Molecular Biotechnology (IPMB), Bioinformatics Division, University of Heidelberg, Heidelberg, 6, Germany.
8
Theoretical Bioinformatics Division, German Cancer Research Center, Heidelberg, 69120, Germany.
9
Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain. manuel.serrano@irbbarcelona.org.
10
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, 08028, Spain. manuel.serrano@irbbarcelona.org.
11
Virus-Host Interaction Group, Department of Infectious Diseases/Virology, Heidelberg University Hospital, Cluster of Excellence CellNetworks, Heidelberg, 69120, Germany. dirk.grimm@bioquant.uni-heidelberg.de.
12
BioQuant, University of Heidelberg, Heidelberg, 69120, Germany. dirk.grimm@bioquant.uni-heidelberg.de.
13
German Center for Infection Research (DZIF), Partner site Heidelberg, Heidelberg, 69120, Germany. dirk.grimm@bioquant.uni-heidelberg.de.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center