scholarly journals Systemic human minidystrophin gene transfer improves functions and life span of dystrophin and dystrophin/utrophin-deficient mice

2008 ◽  
Vol 27 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Bing Wang ◽  
Juan Li ◽  
Freddie H. Fu ◽  
Xiao Xiao
Keyword(s):  
Gene Transfer ◽  
Life Span ◽  
Deficient Mice

scholarly journals Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice

Gene Therapy ◽  
2019 ◽  
Vol 26 (3-4) ◽  
pp. 121-130 ◽  
Author(s):  
Eleonora Leggiero ◽  
Giuseppe Labruna ◽  
Laura Iaffaldano ◽  
Barbara Lombardo ◽  
Adelaide Greco ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Ldl Receptor ◽  
Chimeric Protein ◽  
Aortic Atherosclerosis ◽  
Deficient Mice

scholarly journals Effects of Vector Backbone and Pseudotype on Lentiviral Vector-mediated Gene Transfer: Studies in Infant ADA-Deficient Mice and Rhesus Monkeys

2014 ◽  
Vol 22 (10) ◽  
pp. 1803-1816 ◽  
Author(s):  
Denise Carbonaro Sarracino ◽  
Alice F Tarantal ◽  
C Chang I. Lee ◽  
Michele Martinez ◽  
Xiangyang Jin ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Rhesus Monkeys ◽  
Lentiviral Vector ◽  
Vector Backbone ◽  
Deficient Mice

Gene transfer into normal human hematopoietic cells using in vitro and in vivo assays

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 624-634 ◽  
Author(s):  
JE Dick ◽  
S Kamel-Reid ◽  
B Murdoch ◽  
M Doedens
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Gene Transfer ◽  
Hematopoietic Cells ◽  
Human Stem Cells ◽  
In Vivo Assays ◽  
Genetically Manipulated ◽  
Deficient Mice

Abstract The ability to transfer new genetic material into human hematopoietic cells provides the foundation for characterizing the organization and developmental program of human hematopoietic stem cells. It also provides a valuable model in which to test gene transfer and long-term expression in human hematopoietic cells as a prelude to human gene therapy. At the present time such studies are limited by the absence of in vivo assays for human stem cells, although recent descriptions of the engraftment of human hematopoietic cells in immune-deficient mice may provide the basis for such an assay. This study focuses on the establishment of conditions required for high efficiency retrovirus- mediated gene transfer into human hematopoietic progenitors that can be assayed in vitro in short-term colony assays and in vivo in immune- deficient mice. Here we report that a 24-hour preincubation of human bone marrow in 5637-conditioned medium, before infection, increases gene transfer efficiency into in vitro colony-forming cells by sixfold; interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) provide the same magnitude increase as 5637-conditioned medium. In contrast, incubation in recombinant growth factors IL-1, IL-3, and granulocyte- macrophage colony-stimulating factor increases gene transfer efficiency by 1.5- to 3-fold. Furthermore, preselection in high concentrations of G418 results in a population of cells significantly enriched for G418- resistant progenitors (up to 100%). These results, obtained using detailed survival curves based on colony formation in G418, have been substantiated by directly detecting the neo gene in individual colonies using the polymerase chain reaction. Using these optimized protocols, human bone marrow cells were genetically manipulated with a neo retrovirus vector and transplanted into immune-deficient bg/nu/xid mice. At 1 month and 4 months after the transplant, the hematopoietic tissues of these animals remained engrafted with genetically manipulated human cells. More importantly, G418-resistant progenitors that contained the neo gene were recovered from the bone marrow and spleen of engrafted animals after 4 months. These experiments establish the feasibility of characterizing human stem cells using the unique retrovirus integration site as a clonal marker, similar to techniques developed to elucidate the murine stem cell hierarchy.

Effect of anti-oxidative enzyme gene-transfer on endothelial cell function of apolipoprotein-E deficient mice

2006 ◽  
Vol 45 (3) ◽  
pp. e73-e74
Author(s):  
P-J. Guns ◽  
T. Van Assche ◽  
W. Verreth ◽  
P. Fransen ◽  
B. Mackness ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Gene Transfer ◽  
Apolipoprotein E ◽  
Cell Function ◽  
Oxidative Enzyme ◽  
Endothelial Cell Function ◽  
Enzyme Gene ◽  
Deficient Mice

scholarly journals 764. Dosing and Re-Administration of Intravenous Lentiviral Vector for Liver-Directed Gene Transfer in Young Rhesus Monkeys and ADA-Deficient Mice

2016 ◽  
Vol 24 ◽  
pp. S302-S303
Author(s):  
Denise A. Carbonaro-Sarracino ◽  
Alice F. Tarantal ◽  
Chang I. Lee ◽  
Michael L. Kaufman ◽  
Michele Martinez ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Rhesus Monkeys ◽  
Lentiviral Vector ◽  
Deficient Mice

scholarly journals Partial Reversal of Tissue Calcification and Extension of Life Span following Ammonium Nitrate Treatment of Klotho-Deficient Mice

2016 ◽  
Vol 41 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Christina B. Leibrock ◽  
Martina Feger ◽  
Jakob Voelkl ◽  
Ursula Kohlhofer ◽  
Leticia Quintanilla-Martinez ◽  
...  
Keyword(s):  
Life Span ◽  
Ammonium Nitrate ◽  
Tissue Calcification ◽  
Nitrate Treatment ◽  
Deficient Mice ◽  
Partial Reversal

A Novel Role of Coagulation Proteases on Viral-Based Gene Transfer Efficacy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 691-691
Author(s):  
Joerg Schuettrumpf ◽  
Jianxiang Zou ◽  
Shin Jen Tai ◽  
Alexander Schlachterman ◽  
Kian Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Knockout Mice ◽  
Viral Vectors ◽  
Hemophilia B ◽  
Gene Copy ◽  
Dependent Manner ◽  
Deficient Mice

Abstract Coagulation proteases are crucial for hemostasis and have also been implicated in inflammatory responses, blood vessel formation, and tumor cell metastasis. Cellular responses triggered by proteases are mediated by protease-activated receptors (PAR). Adeno-associated virus (AAV)-2 vectors hold promise for the treatment of several diseases and were already tested in Phase I studies for hemophilia B following intramuscular or hepatic artery deliveries. Previously, we determined an unexpected inhibitory effect (60–70% downregulation) on AAV-2 and adenovirus mediated gene transfer by thrombin- or FXa inhibitors. These results were independent of mouse strain, transgene product, or vector promoter, and gene expression by vectors of alternate serotypes AAV-5 or -8, which do not share cellular receptors with AAV-2, were not affected by any drug. Here we present in vivo evidence of a novel role of coagulation proteases and PARs in modulating gene transfer by viral vectors. We tested AAV-2 gene transfer efficacy in (a) animal models for proteases deficiency [FX and FIX deficient animals], (b) PAR-1 or PAR-2 deficient mice, (c) and following in vivo activation of PARs. FX knockout mice with residual activity of only 1–3% of normal (n=9) were injected with AAV-2-human(h)FIX vector and compared to littermates with FX levels of 50% (n=4). FIX expression levels were 2-fold lower among FX-deficient mice compared to controls (p<0.03). The second model, FIX deficient mice, received AAV expressing α1-antitrypsin (AAT-1). Severe hemophilia B models due to large-gene deletion (n=5) or missense mutation (R180T) in the FIX gene (n=3, <1% FIX) were compared to littermate controls with normal FIX levels (n=6). The results showed that AAT-1 levels among hemophilia B mice were 2-fold lower than in controls (24 vs 48 ng/ml, p<0.05, respectively). Because PAR activation by thrombin enhances αVβ5 (co-receptor for AAV-2 and adenovirus)-dependent cellular function (JBC 276:10952) we hypothesized that PAR modulates AAV-2 gene transfer. Homozygous (−/−) or heterozygous deficient (+/−) PAR-1 (n=24) or PAR-2 (n=25) mice received AAV-2-hF.IX and were compared to littermate controls (+/+). FIX levels among PAR-1 controls (1.9 μg/ml) were comparable to levels obtained among heterozygotes but higher than in homozygotes (1.1 μg/ml, p<0.02). Similarly, PAR-2 deficient mice presented 2-fold lower FIX levels than controls (0.7 vs 1.3 μg/ml, p<0.02) whereas heterozygous mice presented intermediate levels. To further confirm the role of PARs in AAV-2 gene transfer we activated PARs prior to AAV-2 injection. C57BL/6 mice received specific peptide agonists at doses ranging from 10 to 60 μM/kg (n=4 per dose and per peptide) and were compared to controls receiving scramble peptide. FIX levels increased 1.5 to 5-fold in a dose-dependent manner and the activation of PAR-1 and -2 simultaneously was superior to single peptide. Gene copy monitoring revealed low vector uptake by livers of PAR knockout mice while activation of PARs increased uptake. In conclusion, these data demonstrated a novel in vivo role of coagulation proteases and PARs on viral vectors (AAV-2 and adenovirus)-mediated gene expression and provide an alternative target to modulate gene therapy strategies.

Sign in / Sign up

Export Citation Format

Share Document