Amphotropic retroviruses with a hybrid long terminal repeat as a tool for gene therapy of cystic fibrosis

Wilke, Martina; Bout, Bram; Verbeek, Elly; Kappers, Wendy; Verkerk, T.; Valerio, D.; Scholte, Bob J.

doi:10.1016/s0006-291x(05)81477-9

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…One of the parameters that can, at least for supernatant infections, be expected to influence the efficiency of retroviral transduction is the virus-to-target cell ratio. This can be deduced from the observation by Wilke et al (1992), who found a linear relation between amphotropic retrovirus-titer and gene transfer efficiency to NIH-3T3 cells up to a maximum of approximately 10% transduced cells, suggesting that only at high virus concentration do other factors than the titer become limiting. It is, however, unresolved whether such a relation between virus titer and transduction efficiency also exists for a co-cultivation setting, where target cells are constantly subjected to infection with freshly produced virus particles.…”

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confidence: 87%

Retrovirus-Mediated Gene Transfer into Rhesus Monkey Hematopoietic Stem Cells: The Effect of Viral Titers on Transduction Efficiency

Beusechem

Bakx²,

Kaptein³

et al. 1993

Human Gene Therapy

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We have generated a cell line, designated POAM-P1, shedding amphotropic recombinant retroviruses carrying the human adenosine deaminase (hADA) gene. It exhibits a 1 log increased retrovirus titer on NIH-3T3 cells and a five-fold more efficient transduction of human ADA-deficient T lymphocytes, as compared to the previously generated cell line POC-1 which produces the same recombinant hADA retrovirus. To study whether the titer of retrovirus-producing cell lines influences the transduction efficiency of hematopoietic stem cells in a co-culture setting, we compared the POAM-P1 and POC-1 cell lines with respect to their gene transfer efficiency on rhesus monkey bone marrow. Following co-cultivation of rhesus monkey bone marrow with POAM-P1 cells, successful transduction could be demonstrated in approximately 10% of myeloid progenitor colonies (CFU-C) and 0.1% of peripheral blood mononuclear cells (PBMC) and granulocytes in vivo until > 1 year after autologous transplantation. In addition, the presence of functional hADA enzyme was detected in red blood cells, PBMC, and granulocytes. Monkeys receiving POC-1 co-cultured bone marrow carried transduced blood cells for > 2 years after transplantation. Despite the higher retrovirus titer of POAM-P1 cells as compared to POC-1 cells, no difference was observed in gene transfer efficiency into CFU-C and long-term repopulating stem cells. This shows that in our co-cultivation procedure the retrovirus titer was not limiting the transduction efficiency of primate hematopoietic stem cells.

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mentioning

confidence: 87%

Retrovirus-Mediated Gene Transfer into Rhesus Monkey Hematopoietic Stem Cells: The Effect of Viral Titers on Transduction Efficiency

Beusechem

Bakx²,

Kaptein³

et al. 1993

Human Gene Therapy

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“…In order to use a murine virus for gene transfer to humans, entry must occur through a more general, or amphotropic, receptor as opposed to the more efficient speciesspecific, or ecotropic, receptor [13,14]. Alternatively, more promiscuous exogenous proteins may be used for this purpose [15].…”

Section: The Viruses 41 Oncogenic Retrovirusesmentioning

confidence: 99%

Viral gene delivery

Strayer¹

1999

Expert Opinion on Investigational Drugs

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Experimental studies of viral gene delivery generally support the principle that virus-mediated gene transfer is indeed possible. However, the field of gene therapy has not yet been realised as a practicable clinical intervention. The delay in translation of laboratory work to clinical utility largely reflects the inability of gene delivery vectors to convey adequate genetic material to a desired location, with adequate durability and low enough toxicity to be effective. Current studies of viral gene therapy vehicles have focused on re-engineering viruses being tested as vectors at present, treating the host to facilitate viral gene transfer and the development of new vectors. Initial enthusiasm for oncoretroviral and adenoviral vectors has cooled, while adeno-associated virus and lentiviral vectors are attracting more interest. Experimental studies with modified SV40-based vectors have also been very promising. The future of gene therapy will probably entail using an array of gene delivery vehicles, each with its own strengths and weaknesses. The vector systems will probably be as diverse as the applications to which they will be put.

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Cystic Fibrosis

Samuelson

1995

Medicine

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Amphotropic retroviruses with a hybrid long terminal repeat as a tool for gene therapy of cystic fibrosis

Cited by 5 publications

References 17 publications

Retrovirus-Mediated Gene Transfer into Rhesus Monkey Hematopoietic Stem Cells: The Effect of Viral Titers on Transduction Efficiency

Retrovirus-Mediated Gene Transfer into Rhesus Monkey Hematopoietic Stem Cells: The Effect of Viral Titers on Transduction Efficiency

Viral gene delivery

Cystic Fibrosis

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