scholarly journals Intrathecal Injection of Helper-Dependent Adenoviral Vectors Results in Long-Term Transgene Expression in Neuroependymal Cells and Neurons

2011 ◽  
Vol 22 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Scott Dindot ◽  
Pasquale Piccolo ◽  
Nathan Grove ◽  
Donna Palmer ◽  
Nicola Brunetti-Pierri
Keyword(s):  
Transgene Expression ◽  
Intrathecal Injection ◽  
Adenoviral Vectors

scholarly journals Helper-dependent adenoviral vectors in experimental gene therapy.

2005 ◽  
Vol 52 (3) ◽  
pp. 589-599 ◽  
Author(s):  
Alicja Józkowicz ◽  
Józef Dulak
Keyword(s):  
Gene Therapy ◽  
Transgene Expression ◽  
Inflammatory Responses ◽  
Adenoviral Vectors ◽  
Strong Immune Response ◽  
Basic Features ◽  
High Level ◽  
Effective Transfer

In the majority of potential applications gene therapy will require an effective transfer of a transgene in vivo resulting in high-level and long-term transgene expression, all in the absence of significant toxicity or inflammatory responses. The most efficient vehicles for delivery of foreign genes to the target tissues are modified adenoviruses. Adenoviral vectors of the first generation, despite the high infection efficacy, have an essential drawback: they induce strong immune response, which leads to short term expression of the transgene, and limits their usefulness in clinical trials. In contrast, helper-dependent adenoviral vectors (HdAd) lacking all viral coding sequences display only minimal immunogenicity and negligible side-effects, allowing for long-term transgene expression. Thus, HdAd vehicles have become the carrier of choice for adenoviral vector-mediated experimental gene therapy, effectively used in animal models for delivery of transgenes into the liver, skeletal muscle, myocardium or brain. Strong and long-lasting expression of therapeutic genes has allowed for successful treatment of dyslipidemias, muscular dystrophy, obesity, hemophilia, and diabetes. Additionally, the large cloning capacity of HdAd, up to 37 kb, facilitates the use of physiologically regulated, endogenous promoters, instead of artificial viral promoter sequences. This enables also generation of the single vectors expressing multiple genes, which can be potentially useful for treatment of polygenic diseases. In this review we characterize the basic features of HdAd vectors and describe some of their experimental and potential clinical applications.

Long-term transgene expression can be mediated in the brain by adenoviral vectors when powerful neuron-specific promoters are used

2003 ◽  
Vol 5 (7) ◽  
pp. 554-559 ◽  
Author(s):  
Colin P. J. Glover ◽  
Alison S. Bienemann ◽  
Margaret Hopton ◽  
Thomas C. Harding ◽  
James N. Kew ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Adenoviral Vectors ◽  
The Brain
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