Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors

Eglitis, Martin A.; Kantoff, PW; Jd, Jolly; Jones, J. B.; Anderson, W. French; Cd, Lothrop

doi:10.1182/blood.v71.3.717.717

Cited by 35 publications

(3 citation statements)

References 22 publications

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“…Inhibition of HIV replication in varying degrees by antisense RNA as well as sense RNA has been shown [15,26,29]. We now report that using a murine retroviral vector [10,11,13], an anti-SIV gene can be efficiently delivered into a cultured human CD 4 + cell line in which it can effectively block SIV and HIV replication. This report represents the first step towards the application of antisense/sense gene therapy approach in an animal model.…”

Section: Introductionmentioning

confidence: 89%

Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer

Tung

Daniel

1993

Archives of Virology

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To test the feasibility of gene therapy for AIDS patients, an animal model is needed to evaluate the efficacy and safety of this approach. Antiviral genes (encoding antisense RNA or viral protein) derived from Simian immunodeficiency virus (SIV) were efficiently targeted into CD4+ lymphocytes through retroviral-mediated gene transfer. After challenging with infectious viruses, the transduced lymphocytes that received antiviral genes were not only protected from SIV infection, but also from infection with HIV, for at least 25 days. Furthermore, little or no cytolytic effect (syncytium formation) was observed in the protected cells. These data demonstrated that SIV or HIV replication could be effectively blocked by antisense sequence(s) or negative dominant factors which were introduced into targeted cells through retroviral-mediated gene transfer.

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Section: Introductionmentioning

confidence: 89%

Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer

Tung

Daniel

1993

Archives of Virology

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“…Cocultivation of amphotropic producer cells with canine bone marrow cells [29,30] resulted in approximately 40% provirus positive CFU-GM as established by drug resistance. In contrast, only 5% drug resistant CFU-GM were scored using supernatant transduction [31]. These initial experiments indicated that, similar to the murine situation, cocultivation was superior to supernatant transduction.…”

Section: Gene Therapy Studies In Nonhuman Primates and Humansmentioning

confidence: 99%

Retroviral Stem Cell Gene Therapy

et al. 1997

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Long-term in vivo gene transfer studies in mice have shown that recombinant murine retroviruses are able to infect murine hemopoietic stem cells with high efficiency. Taken together the results indicated that the proviral structure was present at high frequency in circulating hemopoietic cells resulting in significant expression levels. Because of the success of these murine studies, it was believed that gene therapy would soon be applicable to treat a wide variety of congenital or acquired human diseases associated with the hemopoietic system. However, results from gene transfer studies in nonhuman primates and first human clinical trails have indicated that murine retrovirus infection of primate hemopoietic stem cells is inefficient. Although there are essential differences between the murine and primate gene therapy studies with respect to the recombinant viruses and transduction protocols used, these differences cannot solely account for the differences observed in infection efficiency. Therefore, in recent years effort has been spent on the identification of factors limiting retroviral transduction of primate hemopoietic stem cells. Increasing knowledge concerning hemopoiesis and retroviral infection has helped in identifying a number of limiting factors. Novel transduction strategies and tools have been generated which attempt to circumvent these limiting factors. These factors as well as the strategies that showed increased retroviral infection of primate hemopoietic stem cells will be discussed.

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“…Several studies have recently demonstrated that a foreign gene can be transferred into murine (2, 10,11,13,15,23,24,27,28,40), canine (16,38), primate (4,22), or human (25) hematopoietic progenitors and stem cells by using retroviral vectors. This technology holds promise for potential somatic cell genetic therapy, or it could be a powerful tool for analyzing the dynamics of somatic cells such as hematopoietic cells.…”

mentioning

confidence: 99%

A new retrovirus packaging cell for gene transfer constructed from amplified long terminal repeat-free chimeric proviral genes

Takahara

Hamada

Housman

1992

J Virol

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The retroviral gene transfer system is a powerful tool for somatic gene therapy. A retroviral stock with a high viral titer and lacking replication-competent virus (RCV) is desirable for this type of gene transfer. To fulfill these requirements, we made a new packaging cell line, designated ampli-GPE. To reduce the homology between proviral DNA in the packaging cell and retroviral vector, the gag-pol and env genes of Moloney murine leukemia virus were separated onto two different plasmids, pGP-KV and pENV-KV, respectively, in which the 5' long terminal repeat and the 3' long terminal repeat had been replaced by the mouse metallothionein I promoter or the human 13-globin gene containing the polyadenylation site as control units for the gag-pol and env genes. In addition, these plasmids contained 69%o of the bovine papillomavirus gene for gene amplification to obtain production of virus at a high titer. NIH 3T3 clones containing approximately 20 to 50 copies of the gag-pol and env genes were selected and designated ampli-GPE. When ampli-GPE was transfected with the N2 vector or pZipNeoSV(DHFR) derived from pZipNeoSV(X)1, we established clones producing titers of 5 x 106 and 1 x 106 CFU/ml, respectively. There was no sign of RCV generation in any virus-producing cells from ampli-GPE. However, virus-producing cells derived from 12 cells transfected with N2 did generate RCV. Thus, we showed that ampli-GPE, possessing the minimum complement of proviral genes, has potential for the development of a gene transfer system.

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Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors

Cited by 35 publications

References 22 publications

Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer

Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer

Retroviral Stem Cell Gene Therapy

A new retrovirus packaging cell for gene transfer constructed from amplified long terminal repeat-free chimeric proviral genes

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