TY  - JOUR
A1  - Bayin, N. Sumru
A1  - Modrek, Aram S.
A1  - Dietrich, August
A1  - Lebowitz, Jonathan
A1  - Abel, Tobias
A1  - Song, Hae-Ri
A1  - Schober, Markus
A1  - Zagzag, David
A1  - Buchholz, Christian
A1  - Chao, Moses V.
A1  - Placantonakis, Dimitris G.
T1  - Selective lentiviral gene delivery to CD133-expressing human glioblastoma stem cells
T2  - PLoS One
N2  - Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/36436
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-364364
SN  - 1932-6203
N1  - opyright: © 2014 Bayin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (12):e116114
PB  - PLoS
CY  - Lawrence, Kan.
ER  -