Intravenous injection of a foamy virus vector to correct canine SCID-X1

Burtner, Christopher R.; Beard, Brian C.; Kennedy, Douglas R.; Wohlfahrt, Martin E.; Adair, Jennifer E.; Trobridge, Grant D.; Scharenberg, Andrew M.; Torgerson, Troy R.; Rawlings, David J.; Felsburg, Peter J.; Kiem, Hans Peter

doi:10.1182/blood-2013-11-538926

Cited by 36 publications

(48 citation statements)

References 41 publications

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“…Strikingly, a majority of gene marking (70% to 90%) in peripheral blood came from the PGK.gC.FV vector in both animals, whereas marking from the EF1a.gC.FV vector comprised only a small fraction (5% to 10%; Figure 1C). Interestingly, the early kinetics of gene marking in peripheral blood lymphocytes in these 2 animals was substantially improved as compared with animals treated with the EF1a.gC.FV vector in our previous study 30 (R2202 and R2203; Table 1). As shown in Figure 2C, the fraction of gene-corrected peripheral lymphocytes reached 40% in both R2258 and R2260 at 6 weeks postinjection, as compared with ,5% for the EF1a.gC.FV-treated animals 30 (compare blue and orange lines).…”

Section: Resultsmentioning

confidence: 70%

“…30 Surface interleukin-2 (IL-2) receptor gC expression was determined by staining with APC anti-human CD132 antibody clone TUGh4 (Biolegend, San Diego, CA). Blood was collected in EDTA or heparin tubes, subjected to hemolysis, and washed in phosphate-buffered saline plus 2% fetal bovine serum.…”

Section: Determination Of In Vivo Gene Marking and Phenotype Analysismentioning

confidence: 99%

“…FV vector long terminal repeat-genome junctions were amplified by modified genomic sequencing PCR as described. 30 Resulting sequence libraries were subjected to pairedend Illumina MiSeq platform sequencing. RISs were identified using a bioinformatic method as previously described in detail.…”

Section: Foamy Ris Analysismentioning

confidence: 99%

“…20,[27][28][29] We previously demonstrated the feasibility of in vivo gene therapy in canine SCID-X1 with IV injection of FV vector expressing human codon optimized gC driven by the short elongation factor-1 a promoter (EF1a; EF1a.gC.FV). 30 Successful lymphocyte expansion was reported in these animals, but clonal diversity and T-cell receptor (TCR) repertoire were low, which prompted further optimization of our method. In the current study, we began by investigating the use of an alternative promoter derived from the human phosphoglycerate kinase (PGK) gene on our FV vector (PGK.gC.FV) and then studied the use of a cell mobilization regimen with granulocyte colony-stimulating factor (G-CSF) and AMD3100 before in vivo FV vector administration.…”

Section: Introductionmentioning

confidence: 99%

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Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy

et al. 2018

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Section: Resultsmentioning

confidence: 70%

Section: Determination Of In Vivo Gene Marking and Phenotype Analysismentioning

confidence: 99%

Section: Foamy Ris Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy

et al. 2018

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“…For instance, recent approaches for treating blood-related diseases consist of direct intravenous administration of SFV viral vectors. Identifying the cellular targets of SFV is critical to better estimate the efficiency and safety of such vectors (19,20).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Cellular Tropism of Gorilla Simian Foamy Virus in Blood of Infected Humans

Rua

Betsem

Montange

et al. 2014

J Virol

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Simian foamy viruses (SFV) are retroviruses that are widespread among nonhuman primates. SFV can be transmitted to humans, giving rise to a persistent infection. Only a few data are available concerning the distribution of SFV in human blood cells. Here we purified blood mononuclear cell subsets from 11 individuals infected with a Gorilla gorilla SFV strain and quantified SFV DNA levels by quantitative PCR. SFV DNA was detected in the majority of the CD8 ؉ , CD4 ؉ T cells were positively correlated with the duration of the infection. Our study shows with a quantitative method that CD8 ؉ , CD4 ؉ , and B lymphocytes are major cellular targets of SFV in the blood of infected humans. IMPORTANCE Investigation of SFV infections in humans is important due to the origin of human immunodeficiency viruses (HIV) and human T cell lymphotropic viruses (HTLV) from cross-species transmission of their simian counterparts to humans. Surprisingly little is known about many aspects of the biology of SFV in infected humans, including quantitative data concerning the cellular targets of SFV in vivo.Here we show that the distribution of SFV DNA among the different leukocyte populations is not homogeneous and that viral load in CD4 ؉ T lymphocytes is correlated with the duration of infection. These new data will help in understanding the biology of retroviral infections in humans and can be useful in the growing field of SFV-based gene therapy.

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Adenovirus vectors in hematopoietic stem cell genome editing

Lieber

2019

FEBS Letters

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Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs have the potential for self-renewal and differentiation into all blood cell lineages. This review presents advances of genome editing in HSCs utilizing adenovirus vectors as delivery vehicles. We focus on capsid-modified, helper-dependent adenovirus vectors that are devoid of all viral genes and therefore exhibit an improved safety profile. We discuss HSC genome engineering for several inherited disorders and infectious diseases including hemoglobinopathies, Fanconi anemia, hemophilia, and HIV-1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34 + cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase-mediated random integration, and targeted homology-directed repair triggered integration into selected genomic safe harbor loci are also reviewed.

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Intravenous injection of a foamy virus vector to correct canine SCID-X1

Abstract: Key Points Intravenous injection of a foamy virus carrying a corrective gene facilitates immune cell development in a canine model of SCID-X1. Integration site analysis revealed polyclonal reconstitution in all dogs with evidence for clonal dominance in at least 1 time point.

Cited by 36 publications

References 41 publications

Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy

Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy

In Vivo Cellular Tropism of Gorilla Simian Foamy Virus in Blood of Infected Humans

Adenovirus vectors in hematopoietic stem cell genome editing

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