Gene transfer into stimulated and unstimulated T lymphocytes by HIV-1-derived lentiviral vectors

Costello, Eithne; Muñoz, Miguel; Buetti, Elena; Meylan, Pra; Diggelmann, Heidi; Thali, Markus

doi:10.1038/sj.gt.3301135

Cited by 77 publications

(69 citation statements)

References 36 publications

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“…In this context, it is notable that the CD8 + cells were transduced 4-6 days following T cell receptor (TCR) activation, a period during which there is a significant secretion of cytokines. 41,42 In contrast, in our lentiviral transduction experiments which were performed at an earlier time-point, 24 h post-TCR activation, and in those reported by Costello and colleagues, 43 performed 48 h after activation, gene transfer efficiencies in CD4 + and CD8 + T cells were equivalent. Moreover, Uckert et al 31 found that CD8 + T cells were transduced very inefficiently with a GALV-pseudotyped MuLV vector following a relatively long prestimulation (4-6 days), while we detected high MuLV-mediated transduction of CD8 + T cells following a 24-h stimulation.…”

Section: Discussionmentioning

confidence: 58%

Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap

et al. 2001

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Retroviral vectors have become the primary tool for gene delivery into hematopoietic cells, including T lymphocytes. Lentiviral vectors offer an advantage over Moloney murine leukemia virus (MuLV) vectors because of their ability to translocate across an intact nuclear membrane and integrate into the genome of nonproliferating cells. We have recently demonstrated that a central strand displacement event, controlled by the central polypurine tract (cPPT) and the central termination sequence (CTS), results in the formation of a central DNA flap which acts as a cis-determinant of HIV-1 genome nuclear import. Here, we show that insertion of this DNA determinant in a classical lentiviral vector resulted in a significantly higher level of transduction in acti-

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Section: Discussionmentioning

confidence: 58%

Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap

et al. 2001

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“…Burns et al 25 demonstrated that a complete omission of polycationic additives during VSV-G pseudotyped retrovirus infection resulted in a 100-fold reduction in the number of normal cells, such as the MDCK cell (canine kidney cell). However, Costello et al 27 recently reported that the VSV-G pseudotyped HIV-1 vector using polybrene only enhanced the transduction efficiency of human T lymphocytes by approximately two times. Furthermore, in all the human cancer cell lines tested in this study, subsequently enhanced gene transfer was not detected when using different kinds of cationic chemicals, including polybrene and different cationic liposomes.…”

Section: Cells Were Inoculated Into 48-well Culture Plates Harvestedmentioning

confidence: 99%

“…23,24 In addition, the VSV-G pseudotyped retrovirus withstands the shearing force encountered during ultracentrifugation when generating highly concentrated virus stocks. [25][26][27] To explore the potential of VSV-G pseudotyped retroviral vector as an effective gene delivery vehicle for cancer gene therapy, the transduction efficiency of the virus was investigated in a variety of human cancer cell lines that originated from different organs, such as human hepatocellular carcinoma cells (SK-Hep1, Hep3B), human brain tumor cells (U251-N, U87-MG), human lung cancer cells (H-460), human breast cancer cells (MCF-7), human gastric cancer cells (YCC-1) and human cervical cancer cells (HeLa). For in vitro experiments, the cells were infected with retroviruses using LacZ as a marker gene and bearing different types of envelope proteins, such as PA317 (amphotropic envelope protein)/LacZ, PG13 (gibbon ape leukemia virus envelope protein)/LacZ.…”

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confidence: 99%

Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor

et al. 2001

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A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells was found to be unsatisfactory. Recently, several research groups have demonstrated the feasibility of a retroviral vector pseudotyped with a vesicular stomatitis virus G (VSV-G) protein. In this study, the potential of VSV-G pseudotyped MLV-based retrovirus was examined as a delivery vehicle in a variety of human cancer cells including brain tumor cells in vitro and in vivo. The transduction efficiency of the 293T/G/GP/LacZ retrovirus in cell culture was superior in most cancer cells, particularly in brain tumor cells, compared with that of other retroviruses, such as PA317-or PG13-derived. The relative growth rate and phosphatidylserine expression level on the plasma mem-

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“…However, some laboratories have noticed that vif and vpu may be required for optimal transduction of the liver [20] and of resting lymphocytes [21]. Moreover, Costello et al [22] have found that production of vectors in the absence of all HIV-1 accessory proteins was accompanied by a 50% decrease in transduction efficiency in activated T cells. A recent report has, however, confirmed that nef, vif, vpr and vpu are not required for the transduction of both resident macrophages and activated B lymphoblasts [23].…”

Section: Removal Of Accessory Genesmentioning

confidence: 99%

Lentiviral vectors: optimization of packaging, transduction and gene expression

Delenda

2004

J. Gene Med.

115

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SummaryGene transfer vectors based on retroviruses including oncogenic retroviruses and lentiviruses provide effective means for the delivery, integration and expression of exogenous genes in mammalian cells. Lentiviral (LV) vectors provide attractive gene delivery vehicles in the context of non-dividing cells. This review summarizes the different optimized LV genetic systems that have been developed to date. In all cases, the production of LV-derived vectors consists of a genetically split gene expression design. The viral elements that are specifically required are (i) the LV packaging helper proteins consisting of at least the gag-pol genes, (ii) the LV transfer vector RNA containing the transgene expression cassette, and (iii) an heterologous glycoprotein. While the genetic requirements and performances of the two former viral elements will be treated herein, the latter element relative to the envelope pseudotyping of LV vectors will not be further described (cf. review by Cosset in this issue).

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Gene transfer into stimulated and unstimulated T lymphocytes by HIV-1-derived lentiviral vectors

Cited by 77 publications

References 36 publications

Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap

Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap

Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor

Lentiviral vectors: optimization of packaging, transduction and gene expression

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