Novel Non-integrating DNA Nano-S/MAR Vectors Restore Gene Function in Isogenic Patient-Derived Pancreatic Tumor Models.

S/MAR antibiotic-free gene supplementation isogenic cells nano-DNA vector non-integrating tumor models

Journal

Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857

Informations de publication

Date de publication:
12 Jun 2020
Historique:
received: 31 03 2020
accepted: 22 04 2020
entrez: 19 5 2020
pubmed: 19 5 2020
medline: 19 5 2020
Statut: epublish

Résumé

We describe herein non-integrating minimally sized nano-S/MAR DNA vectors, which can be used to genetically modify dividing cells in place of integrating vectors. They represent a unique genetic tool, which avoids vector-mediated damage. Previous work has shown that DNA vectors comprising a mammalian S/MAR element can provide persistent mitotic stability over hundreds of cell divisions, resisting epigenetic silencing and thereby allowing sustained transgene expression. The composition of the original S/MAR vectors does present some inherent limitations that can provoke cellular toxicity. Herein, we present a new system, the nano-S/MAR, which drives higher transgene expression and has improved efficiency of establishment,

Identifiants

pubmed: 32420409
doi: 10.1016/j.omtm.2020.04.017
pii: S2329-0501(20)30077-2
pmc: PMC7218229
doi:

Types de publication

Journal Article

Langues

eng

Pagination

957-968

Informations de copyright

© 2020 The Authors.

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Auteurs

Matthias Bozza (M)

DNA Vector Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.

Edward W Green (EW)

Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Elisa Espinet (E)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Alice De Roia (A)

DNA Vector Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.

Corinna Klein (C)

Stem Cells and Metastasis, Hi-Stem Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Vanessa Vogel (V)

Stem Cells and Metastasis, Hi-Stem Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Rienk Offringa (R)

Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

James A Williams (JA)

Nature Technology Corporation, Lincoln, NE 68521, USA.

Martin Sprick (M)

Stem Cells and Metastasis, Hi-Stem Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Richard P Harbottle (RP)

DNA Vector Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.

Classifications MeSH