Improved Hepatic Transduction, Reduced Systemic Vector Dissemination, and Long-Term Transgene Expression by Delivering Helper-Dependent Adenoviral Vectors into the Surgically Isolated Liver of Nonhuman Primates

2006 ◽  
Vol 17 (4) ◽  
pp. 391-404 ◽  
Author(s):  
Nicola Brunetti-Pierri ◽  
Thomas Ng ◽  
David A. Iannitti ◽  
Donna J. Palmer ◽  
Arthur L. Beaudet ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Adenoviral Vectors ◽  
Isolated Liver

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 Transgene Expression up to 7 Years in Nonhuman Primates Following Hepatic Transduction with Helper-Dependent Adenoviral Vectors

2013 ◽  
Vol 24 (8) ◽  
pp. 761-765 ◽  
Author(s):  
Nicola Brunetti-Pierri ◽  
Thomas Ng ◽  
David Iannitti ◽  
William Cioffi ◽  
Gary Stapleton ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Adenoviral Vectors

scholarly journals Long-term doxycycline-regulated transgene expression in the retina of nonhuman primates following subretinal injection of recombinant AAV vectors

2006 ◽  
Vol 13 (5) ◽  
pp. 967-975 ◽  
Author(s):  
Knut Stieger ◽  
Guylène Le Meur ◽  
Françoise Lasne ◽  
Michel Weber ◽  
Jack-Yves Deschamps ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Subretinal Injection

scholarly journals Lack of an Immune Response against the Tetracycline-Dependent Transactivator Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primates after Intramuscular Injection of Recombinant Adeno-Associated Virus

2002 ◽  
Vol 76 (22) ◽  
pp. 11605-11611 ◽  
Author(s):  
David Favre ◽  
Véronique Blouin ◽  
Nathalie Provost ◽  
Radec Spisek ◽  
Françoise Porrot ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Cynomolgus Macaque ◽  
Experimental Period ◽  
Adeno Associated Virus ◽  
Cellular Immune Responses ◽  
Transactivator Protein ◽  
Cellular Immune ◽  
Vector Dna

ABSTRACT We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, and J. M. Heard, Blood 92:1512-1517, 1998). Using the same vector harboring the cynomolgus macaque Epo cDNA instead, the present study evaluated the ability of the tetracycline-regulatable (tetR) system to establish long-term transgene regulation in nonhuman primates. The vector was administered i.m., after which 5-day induction pulses were performed monthly for up to 13 months by using doxycycline (DOX), a tetracycline analog. We show that initial inductions were successful in all individuals and that there was a tight regulation and a rapid deinduction pattern upon DOX withdrawal. For one macaque, regulation of Epo secretion was maintained during the entire experimental period; for the five remaining macaques, secreted Epo became indistinguishable from endogenous Epo upon repeated DOX inductions. We investigated the mechanism involved and showed that, except in the animal in which secretion persisted, delayed humoral and cellular immune responses were directed against the rtTA transactivator protein associated with the reduction of vector DNA in transduced muscles. This study provides some evidence that, when the immune system is not mobilized against the rtTA transactivator, the tetR-regulatable system is able to support long-term transgene regulation in the context of an rAAV in nonhuman primates. In addition, our results suggest potential improvements for vector design.

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

Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates

Hepatology ◽  
2008 ◽  
Vol 49 (3) ◽  
pp. 950-959 ◽  
Author(s):  
Ibrahim Dagher ◽  
Tuan Huy Nguyen ◽  
Marie-Thérèse Groyer-Picard ◽  
Panagiotis Lainas ◽  
Sylvie Mainot ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Portal Embolization
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