scholarly journals Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

2012 ◽  
Vol 20 (7) ◽  
pp. 1410-1416 ◽  
Author(s):  
Federico Mingozzi ◽  
Yifeng Chen ◽  
Samuel L Murphy ◽  
Shyrie C Edmonson ◽  
Alex Tai ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Humoral Immunity ◽  
Nonhuman Primate ◽  
Hemophilia B ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Pharmacological Modulation

Efficient Transduction of Common Marmoset (Callithrix jacchus) Hematopoietic and Embryonic Stem Cells Using Foamyvirus Vectors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5530-5530
Author(s):  
Peter A. Horn ◽  
Melanie Wurm ◽  
Ryo Kurita ◽  
Tomoko Yokoo ◽  
Rainer Blasczyk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Gene Transfer ◽  
Nonhuman Primate ◽  
Embryonic Stem ◽  
Common Marmoset ◽  
Transduction Efficiency ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Efficient Gene

Abstract Preclinical animal models are important for evaluating the safety and therapeutic efficacy of new therapeutic modalities such as gene therapy. From the different large animal models, nonhuman primate models have emerged over the last decades as highly desirable experimental systems from both a pathophysiologic and pharmacokinetic viewpoint and the study of nonhuman primates has provided important information on the efficacy and safety of gene therapy systems in vivo prior to human trials. The common marmoset (Callithrix jacchus) has the advantage that it is a small, and thus relatively inexpensive nonhuman primate model. Currently, very little data on the transduction efficiency of foamyviral vectors for gene transfer into marmoset stem cells exists. We therefore performed a direct comparison using identically designed gammaretroviral, lentiviral and foamyviral vector constructs expressing the enhanced green fluorescent protein (EGFP) from the spleen focus forming virus (SFFV) promoter pseudotyped with either the modified human foamy virus (HFV) envelope EM140 or the G-protein of vesicular stomatitis virus (VSV-G) for the transduction of common marmoset embryonic stem cells (CMES) as well as marmoset CD34+ hematopoietic progenitor cells. Virus stocks of these vectors were prepared by polyethyleneimine-mediated transfection of 293T cells and concentrated approximately 10-fold by centrifugation for 4 hours at 10.000 g at 4°C. Three different target cell populations were transduced: common marmoset embryonic stem cells (CMES) or cryopreserved CD34-enriched cells from bone marrow of a common marmoset either after a two-day prestimulation in the presence of IL-6, FLT3L, cSCF and TPO at a concentration of 100 ng/mL each, or after overnight incubation with 100 ng/mL SCF only. Equal numbers of cells were exposed to the four different vector preparations for 14 hours in 12-well dishes coated with CH-296. The read-out was based on fluorescence microscopy of colonies plated in methyl cellulose as well as flow cytometry (FACS). Foamyviral vectors with the foamyviral envelope were the most efficient gene transfer tool for marmoset hematopoietic CD34-positive cells with stable transduction rates of over 80% as assessed by flow cytometry at both 2 or 7 days after the end of transduction and on average 88% transduction efficiency into colony forming cells (CFU-C). Transduction of CFU-C with all other vector preparations was below 60%. In CMES, initial gene transfer rates of over 80% were achieved with the VSV-G pseudotype lentiviral vector, however, expression decreased to 13% after 7 days. In contrast, the foamyviral vector pseudotyped with the foamyviral envelope decreased only from 49% to 24% after 7 days. In conclusion, we achieved stable viral gene transfer and expression in CMES cells as well as highly efficient gene transfer into common marmoset hematopoietic CD34 positive cells using foamyviral vectors. These results suggest that foamyviral vectors may be highly feasible vectors for stem cell gene transfer and thus set the stage for a more detailed analysis of this vector system in transplantation studies in this nonhuman primate model.

scholarly journals Generation and in vivo evaluation of IL10-treated dendritic cells in a nonhuman primate model of AAV-based gene transfer

2014 ◽  
Vol 1 ◽  
pp. 14028 ◽  
Author(s):  
Aurélie Moreau ◽  
Céline Vandamme ◽  
Mercedes Segovia ◽  
Marie Devaux ◽  
Mickaël Guilbaud ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Gene Transfer ◽  
Nonhuman Primate ◽  
Nonhuman Primate Model ◽  
In Vivo Evaluation ◽  
Primate Model

scholarly journals Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2334-2341 ◽  
Author(s):  
Federico Mingozzi ◽  
Nicole C. Hasbrouck ◽  
Etiena Basner-Tschakarjan ◽  
Shyrie A. Edmonson ◽  
Daniel J. Hui ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Transfer ◽  
Nonhuman Primate ◽  
Drug Regimen ◽  
Factor Ix ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Adeno Associated Virus ◽  
Inhibitory Antibodies

Adeno-associated virus (AAV)–mediated gene transfer of factor IX (F.IX) to the liver results in long-term expression of transgene in experimental animals, but only short-term expression in humans. Loss of F.IX expression is likely due to a cytotoxic immune response to the AAV capsid, which results in clearance of transduced hepatocytes. We used a nonhuman primate model to assess the safety of AAV gene transfer coupled with an anti–T-cell regimen designed to block this immune response. Administration of a 3-drug regimen consisting of mycophenolate mofetil (MMF), sirolimus, and the anti–IL-2 receptor antibody daclizumab consistently resulted in formation of inhibitory antibodies to human F.IX following hepatic artery administration of an AAV-hF.IX vector, whereas a 2-drug regimen consisting only of MMF and sirolimus did not. Administration of daclizumab was accompanied by a dramatic drop in the population of CD4+CD25+FoxP3+ regulatory T cells (Tregs). We conclude that choice of immunosuppression (IS) regimen can modulate immune responses to the transgene product upon hepatic gene transfer in subjects not fully tolerant; and that induction of transgene tolerance may depend on a population of antigen-specific Tregs.

Maternal High-Fat Diet Persistently Alters Bone Marrow Immune Cell Proportions and Function in a Nonhuman Primate Model

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 222-OR
Author(s):  
MICHAEL J. NASH ◽  
TAYLOR K. SODERBORG ◽  
RACHEL C. JANSSEN ◽  
ERIC M. PIETRAS ◽  
JACOB E. FRIEDMAN
Keyword(s):  
Bone Marrow ◽  
Nonhuman Primate ◽  
High Fat Diet ◽  
Immune Cell ◽  
High Fat ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
And Function

scholarly journals Reperfusion plus Selective Intra-arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Stroke

2020 ◽  
Author(s):  
Di Wu ◽  
Yongjuan Fu ◽  
Longfei Wu ◽  
Mitchell Huber ◽  
Jian Chen ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Nonhuman Primate Model ◽  
Primate Model

Robotic Assessment of Upper Limb Function in a Nonhuman Primate Model of Chronic Stroke

2021 ◽  
Author(s):  
Yining Chen ◽  
Meredith C. Poole ◽  
Shelby V. Olesovsky ◽  
Allen A. Champagne ◽  
Kathleen A. Harrison ◽  
...  
Keyword(s):  
Upper Limb ◽  
Nonhuman Primate ◽  
Chronic Stroke ◽  
Nonhuman Primate Model ◽  
Limb Function ◽  
Primate Model ◽  
Upper Limb Function

scholarly journals Transcriptomic phases of periodontitis lesions using the nonhuman primate model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeffrey L. Ebersole ◽  
Radhakrishnan Nagarajan ◽  
Sreenatha Kirakodu ◽  
Octavio A. Gonzalez
Keyword(s):  
Gene Expression ◽  
Nonhuman Primate ◽  
Gingival Crevicular Fluid ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Lesion Detection ◽  
Gingival Tissue ◽  
Specific Gene ◽  
Nonhuman Primate Model ◽  
Primate Model

AbstractWe used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12–22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n = 6049), early progression (n = 4893), and late progression (n = 5078) of disease, with the preponderance being up-regulated. Additionally, 1918 genes were altered in expression with disease resolution, skewed towards down-regulation. Assessment of the genes demonstrated specific profiles of epithelial, bone/connective tissue, apoptosis/autophagy, metabolism, regulatory, immune, and inflammatory responses that were related to health, stages of disease, and tissues with resolved lesions. Unique transcriptomic profiles occured during the kinetics of the periodontitis lesion exacerbation and remission. We delineated phase specific gene expression profiles of the disease lesion. Detection of these gene products in gingival crevicular fluid samples from human disease may contribute to a better understanding of the biological dynamics of the disease to improve patient management.

Sign in / Sign up

Export Citation Format

Share Document