Use of Recombinant Adenovirus-Mediated Gene Transfer to Study Insulin Action in 3T3L1 Adipocytes

1998 ◽  
pp. 154-156
Author(s):  
L. Gnudi ◽  
B.B. Kahn
Keyword(s):  
Gene Transfer ◽  
Insulin Action ◽  
Recombinant Adenovirus

scholarly journals Intra-arterial Delivery of a Recombinant Adenovirus Does Not Increase Gene Transfer to Tumor Cells in a Rat Model of Metastatic Colorectal Carcinoma

2001 ◽  
Vol 4 (1) ◽  
pp. 29-35 ◽  
Author(s):  
David J. Maron ◽  
Hiroomi Tada ◽  
A.David Moscioni ◽  
John Tazelaar ◽  
Douglas L. Fraker ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Colorectal Carcinoma ◽  
Tumor Cells ◽  
Rat Model ◽  
Recombinant Adenovirus ◽  
Metastatic Colorectal Carcinoma

Gene Transfer to Articular Chondrocytes with Recombinant Adenovirus

2003 ◽  
pp. 235-246 ◽  
Author(s):  
Glyn D. Palmer ◽  
Elvire Gouze ◽  
Jean-Noel Gouze ◽  
Oliver B. Betz ◽  
Christopher H. Evans ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Articular Chondrocytes ◽  
Recombinant Adenovirus

scholarly journals Adenovirus vector infection of chronic lymphocytic leukemia B cells

Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4676-4683 ◽  
Author(s):  
MJ Cantwell ◽  
S Sharma ◽  
T Friedmann ◽  
TJ Kipps
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Transfer ◽  
Hela Cells ◽  
Recombinant Adenovirus ◽  
Lymphocytic Leukemia ◽  
Cross Linking ◽  
Gene Transduction ◽  
Transfer Genes ◽  
Adenovirus Vectors

Adenovirus vectors have several features that make them attractive for potential use in gene therapy, including a broad tissue tropism and an ability to infect quiescent or postmitotic cells. In light of this, we examined whether recombinant adenovirus vectors could transfer genes into neoplastic cells of patients with chronic lymphocytic leukemia (CLL), a leukemia of “resting” B cells. Using high-titer recombinant adenovirus vectors, we found we could transfer genes encoding beta-galactosidase or murine CD80 (B7–1) into the CLL B cells of all patients tested (n = 10). The efficiency of gene transduction into CLL B cells was approximately 100 to 1,000-fold lower than into HeLa cells at any given multiplicity of infection (MOI). At a MOI of 500, 10% to 70% of the CLL B cells from different patients were made to express the transgene, as assessed by multiparameter flow cytometric analysis. Sustained levels of expression with little loss in the percentage of infected cells were maintained for up to 9 days, at which point the analysis was stopped. We found that CLL B cells have markedly lower expression levels of integrins that facilitate internalization of adenovirus particles into target cells, perhaps accounting, in part, for the reduced efficiency of adenovirus-mediated gene transfer compared with that in HeLa cells. Although HeLa cells express high levels of alpha(v)beta5, and detectable amounts of alpha(v)beta3, we find CLL cells from all patients tested express only low amounts of alpha(v)beta3, and no detectable alpha(v)beta5. Activation of CLL cells via CD40 cross-linking enhances expression of alpha(v)beta3, and induces expression of alpha(v)beta5. This phenotypic change is associated with a fivefold increase in the efficiency of adenovirus-mediated gene transfer into such activated CLL B cells. This study demonstrates that adenovirus vectors can transduce genes into CLL B cells and that the efficiency of gene transduction is enhanced by activation via CD40 cross-linking. This is the first demonstration that high proportions of CLL B cells can be made to express a selected transgene, suggesting that such gene transfer methods may become useful for the study of the pathogenesis and/or treatment of this disease.

scholarly journals Recombinant Human Adenovirus: Targeting to the Human Transferrin Receptor Improves Gene Transfer to Brain Microcapillary Endothelium

2000 ◽  
Vol 74 (23) ◽  
pp. 11359-11366 ◽  
Author(s):  
Haibin Xia ◽  
Brian Anderson ◽  
Qinwen Mao ◽  
Beverly L. Davidson
Keyword(s):  
Gene Transfer ◽  
Transferrin Receptor ◽  
Viral Vectors ◽  
Recombinant Adenovirus ◽  
Human Adenovirus ◽  
System Component ◽  
Inborn Errors ◽  
Human Transferrin ◽  
Enzyme Replacement ◽  
Human Transferrin Receptor

ABSTRACT Some inborn errors of metabolism due to deficiencies of soluble lysosomal enzymes cause global neurodegenerative disease. Representative examples include the infantile and late infantile forms of the ceroid lipofuscinoses (CLN1 or CLN2 deficiency, respectively) and mucopolysaccharidoses type VII (MPS VII), a deficiency of β-glucuronidase. Treatment of the central nervous system component of these disorders will require widespread protein or enzyme replacement, either through dissemination of the protein or through dissemination of a gene encoding it. We hypothesize that transduction of brain microcapillary endothelium (BME) with recombinant viral vectors, with secretion of enzyme product basolaterally, could allow for widespread enzyme dissemination. To achieve this, viruses should be modified to target the BME. This requires (i) identification of a BME-resident target receptor, (ii) identification of motifs targeted to that molecule, (iii) the construction of modified viruses to allow for binding to the target receptor, and (iv) demonstrated transduction of receptor-expressing cells. In proof of principal experiments, we chose the human transferrin receptor (hTfR), a molecule found at high density on human BME. A nonamer phage display library was panned for motifs which could bind hTfR. Forty-three clones were sequenced, most of which contained an AKxxK/R, KxKxPK/R, or KxK motif. Ten peptides representative of the three motifs were cloned into the HI loop of adenovirus type 5 fiber. All motifs tested retained their ability to trimerize and bind transferrin receptor, and seven allowed for recombinant adenovirus production. Importantly, the fiber-modified viruses facilitated increased gene transfer (2- to 34-fold) to hTfR expressing cell lines and human brain microcapillary endothelia expressing high levels of endogenous receptor. Our data indicate that adenoviruses can be modified in the HI loop for expanded tropism to the hTfR.

High-efficiency gene transfer to primary T lymphocytes by recombinant adenovirus vectors

2002 ◽  
Vol 260 (1-2) ◽  
pp. 79-89 ◽  
Author(s):  
Zhi Chen ◽  
Matti Ahonen ◽  
Heli Hämäläinen ◽  
Jeffrey M Bergelson ◽  
Veli-Matti Kähäri ◽  
...  
Keyword(s):  
Gene Transfer ◽  
T Lymphocytes ◽  
High Efficiency ◽  
Recombinant Adenovirus ◽  
Adenovirus Vectors

scholarly journals Adenovirus-Mediated Transfer of Tissue-Type Plasminogen Activator Augments Thrombolysis in Tissue-Type Plasminogen Activator–Deficient and Plasminogen Activator Inhibitor-1–Overexpressing Mice

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1527-1534
Author(s):  
Peter Carmeliet ◽  
Jean-Marie Stassen ◽  
Ilse Van Vlaenderen ◽  
Robert S. Meidell ◽  
Désiré Collen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Plasminogen Activator ◽  
Recombinant Adenovirus ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Pai 1

Impaired fibrinolysis, resulting from increased plasminogen activator inhibitor-1 (PAI-1) or reduced tissue-type plasminogen activator (t-PA) plasma levels, may predispose the individual to subacute thrombosis in sepsis and inflammation. The objective of these studies was to show that adenovirus-mediated gene transfer could increase systemic plasma t-PA levels and thrombolytic capacity in animal model systems. Recombinant adenovirus vectors were constructed that express either human wild type or PAI-1–resistant t-PA from the cytomegalovirus (CMV) promoter. Both t-PA-deficient (t-PA−/−) and PAI-1–overexpressing transgenic mice were infected by intravenous injection of these viruses. Intravenous injection of recombinant adenovirus resulted in liver gene transfer, t-PA synthesis, and secretion into the plasma. Virus dose, human t-PA antigen, and activity concentrations in plasma and extent of lysis of a 125I-fibrin–labeled pulmonary embolism were all closely correlated. Plasma t-PA antigen and activity were increased approximately 1,000-fold above normal levels. Clot lysis was significantly increased in mice injected with a t-PA–expressing virus, but not in mice injected with saline or an irrelevant adenovirus. Comparable levels of enzyme activity and clot lysis were obtained with wild type and inhibitor-resistant t-PA viruses. Adenovirus-mediated t-PA gene transfer was found to augment clot lysis as early as 4 hours after infection, but expression levels subsided within 7 days. Adenovirus-mediated transfer of a t-PA gene can effectively increase plasma fibrinolytic activity and either restore (in t-PA–deficient mice) or augment (in PAI-1–overexpressing mice) the thrombolytic capacity in simple animal models of defective fibrinolysis.

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