Gene Transfer to Rodent Brain with Recombinant Adenoviral Vectors: Effects of Infusion Parameters, Infectious Titer, and Virus Concentration on Transduction Volume

1998 ◽  
Vol 150 (1) ◽  
pp. 136-142 ◽  
Author(s):  
A.Lorris Betz ◽  
Parvin Shakui ◽  
Beverly L. Davidson
Keyword(s):  
Gene Transfer ◽  
Adenoviral Vectors ◽  
Virus Concentration ◽  
Rodent Brain ◽  
Infectious Titer

scholarly journals Efficient and Selective Gene Transfer into Primary Human Brain Tumors by Using Single-Chain Antibody-Targeted Adenoviral Vectors with Native Tropism Abolished

2002 ◽  
Vol 76 (6) ◽  
pp. 2753-2762 ◽  
Author(s):  
Victor W. van Beusechem ◽  
Jacques Grill ◽  
D. C. Jeroen Mastenbroek ◽  
Thomas J. Wickham ◽  
Peter W. Roelvink ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Brain Tumors ◽  
Human Brain ◽  
Cancer Gene Therapy ◽  
Adenoviral Vectors ◽  
Receptor Expression ◽  
Normal Brain ◽  
Cancer Gene ◽  
Single Chain

ABSTRACT The application of adenoviral vectors in cancer gene therapy is hampered by low receptor expression on tumor cells and high receptor expression on normal epithelial cells. Targeting adenoviral vectors toward tumor cells may improve cancer gene therapy procedures by providing augmented tumor transduction and decreased toxicity to normal tissues. Targeting requires both the complete abolition of native tropism and the addition of a new specific binding ligand onto the viral capsid. Here we accomplished this by using doubly ablated adenoviral vectors, lacking coxsackievirus-adenovirus receptor and αv integrin binding capacities, together with bispecific single-chain antibodies targeted toward human epidermal growth factor receptor (EGFR) or the epithelial cell adhesion molecule. These vectors efficiently and selectively targeted both alternative receptors on the surface of human cancer cells. Targeted doubly ablated adenoviral vectors were also very efficient and specific with primary human tumor specimens. With primary glioma cell cultures, EGFR targeting augmented the median gene transfer efficiency of doubly ablated adenoviral vectors 123-fold. Moreover, EGFR-targeted doubly ablated vectors were selective for human brain tumors versus the surrounding normal brain tissue. They transduced organotypic glioma and meningioma spheroids with efficiencies similar to those of native adenoviral vectors, while exhibiting greater-than-10-fold-reduced background levels on normal brain explants from the same patients. As a result, EGFR-targeted doubly ablated adenoviral vectors had a 5- to 38-fold-improved tumor-to-normal brain targeting index compared to native vectors. Hence, single-chain targeted doubly ablated adenoviral vectors are promising tools for cancer gene therapy. They should provide an improved therapeutic index with efficient tumor transduction and effective protection of normal tissue.

In Vitro Gene Transfer to Chondrocytes and Synovial Fibroblasts by Adenoviral Vectors

2004 ◽  
pp. 147-164
Author(s):  
Jean-Noel Gouze ◽  
Martin J. Stoddart ◽  
Elvire Gouze ◽  
Glyn D. Palmer ◽  
Steven C. Ghivizzani ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Synovial Fibroblasts ◽  
Adenoviral Vectors

Enhanced Growth inhibition by Combined Gene Transfer of p53 and p16INK4a in Adenoviral Vectors to Lung Cancer Cell Lines

2001 ◽  
Vol 50 (1) ◽  
pp. 67
Author(s):  
Seung Ho Choi ◽  
Kyung Ho Park ◽  
Ja Young Seol ◽  
Chul Gyu Yoo ◽  
Choon Taek Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Transfer ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adenoviral Vectors ◽  
Lung Cancer Cell

Budesonide Enhances Repeated Gene Transfer and Expression in the Lung with Adenoviral Vectors

2001 ◽  
Vol 164 (5) ◽  
pp. 866-872 ◽  
Author(s):  
MARTIN KOLB ◽  
MARK INMAN ◽  
PETER J. MARGETTS ◽  
TOM GALT ◽  
JACK GAULDIE
Keyword(s):  
Gene Transfer ◽  
Adenoviral Vectors

Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer

2006 ◽  
Vol 33 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Gang Niu ◽  
Richard D. Anderson ◽  
Mark T. Madsen ◽  
Michael M. Graham ◽  
Larry W. Oberley ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Sodium Iodide ◽  
Adenoviral Vectors ◽  
Radiological Imaging ◽  
Sodium Iodide Symporter ◽  
Therapeutic Gene

Adenovirus-Mediated Gene Transfer to Mesenchymal Stem Cells: Comparison of the Cytomegalovirus- and Rous Sarcoma Virus-Promoter.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5145-5145
Author(s):  
Weiwen Deng ◽  
Troy A. Giambernardi ◽  
Rick V. Hay ◽  
Daniel W. Pietryga ◽  
Aly S. Abdel-Mageed
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Transfer ◽  
Rous Sarcoma Virus ◽  
Ex Vivo ◽  
Adenoviral Vectors ◽  
Transduction Efficiency ◽  
Cmv Promoter ◽  
Rous Sarcoma ◽  
Sarcoma Virus

Abstract We have compared the efficacy and toxicity of the cytomegalovirus (CMV) promoter and the Rous sarcoma virus (RSV) promoter for expressing genes for adenovirus-mediated gene transfer to mesenchymal stem cells (MSCs). Mouse MSCs (mMSCs) were isolated from the femurs and tibias of 6-week old, female BALB/c mice and ex vivo expanded in MEM-alpha containing 20% fetal bovine serum, 100 u/ml penicillin, 100 μg/ml streptomycin, 250 ng/ml amphotericin B, and 2 mM L-glutamine. To transduce mMSCs with adenovirus, the cells were plated at a density of 10,000 cells/cm2 in 6-well plates and cultured overnight. The cells were counted and then exposed to fresh culture medium containing adenovirus at 0 to 2,000 multiplicities of infection (MOI) for 48 h. Two adenoviral vectors with CMV promoter (Adv/CMV) and two adenoviral vectors with RSV promoter (Adv/RSV) were used in this study. Transduction efficiency and cell survival were then determined. The Adv/CMVs, i.e. AdvCMVlacZ and AdvCMVIL-10, were more potent in terms of transduction efficiency and transgene expression than their corresponding Adv/RSVs, i.e. AdvRSVlacZ and AdvRSVIL-10. However, both vectors exhibit a dose-dependent relationship between the adenoviral vector MOI and the percentage of transgene-expressing cells. Furthermore, no toxicity was observed in Adv/CMV or Adv/RSV transduced mMSCs.

scholarly journals Reduced Inflammatory Reactions to the Inoculation of Helper-Dependent Adenoviral Vectors in Traumatically Injured Rat Brain

2002 ◽  
Vol 22 (8) ◽  
pp. 959-970 ◽  
Author(s):  
Linglong Zou ◽  
Patricia Yotnda ◽  
Tiejun Zhao ◽  
Xiaoqing Yuan ◽  
Yan Long ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Rat Brain ◽  
Neutralizing Antibodies ◽  
Transgene Expression ◽  
First Generation ◽  
High Efficiency ◽  
Adenoviral Vectors ◽  
Tissue Loss ◽  
Inflammatory Reactions

Traumatic brain injury (TBI) causes delayed neuronal deficits that in principle could be prevented by timely intervention with therapeutic genes. However, appropriate vectors for gene transfer to the brain with TBI remain to be developed. First-generation adenoviruses (fgAd) are usually associated with inflammatory and toxic effects when inoculated into brains, despite their high efficiency of gene transfer to these tissues. In this study the authors attempted to determine whether a less immunogenic gene-transfer protocol can be established in the traumatically injured rat brain using helper-dependent adenoviruses (hdAd), a novel adenoviral construct with full deletion of viral coding sequences. Their results show that transgene expression from intrahippocampally inoculated hdAd is maintained for at least 2 months after TBI, in contrast to the much shorter duration of fgAd-mediated gene expression. There was only minimal secretion of proinflammatory IL-1β and TNF-α after inoculation of hdAd. Furthermore, the hdAd-mediated gene expression was associated with less microglial proliferation, astrocytic activation, and macrophage infiltration than observed in fgAd-inoculated brains. There was no additional tissue loss after hdAd inoculation compared with PBS injection. Although both anti-adenoviral and neutralizing antibodies were found in serum after brain inoculation of hdAd, they did not appear to affect transgene expression. The results suggest that hdAd are less immunogenic vectors than conventional adenoviral vectors, and offer improved vehicles for long-term therapeutic transgene transfer to traumatically injured brains.

scholarly journals Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes

Gene Therapy ◽  
2003 ◽  
Vol 10 (13) ◽  
pp. 1089-1098 ◽  
Author(s):  
J Park ◽  
J Ries ◽  
K Gelse ◽  
F Kloss ◽  
K von der Mark ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Bone Regeneration ◽  
Critical Size ◽  
Adenoviral Vectors ◽  
Critical Size Defects
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