Lentiviral vectors: turning a deadly foe into a therapeutic agent

Trono, Didier

doi:10.1038/sj.gt.3301105

Cited by 238 publications

(135 citation statements)

References 35 publications

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“…26 ). Because VSV-G pseudotyped lentiviruses can efficiently introduce new genetic material to a variety of nondividing cells, they are potential vectors for many solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy

et al. 2001

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To evaluate human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase ( HSV -TK ) ± mediated gene therapy, we tested the utility of different viral vectors on three human cell lines DU -145, LNCaP, and PC -3. Our viral vectors were carrying a fusion gene of HSV -TK and green fluorescent protein for accurate determination of the gene transfer rate and its contribution to the treatment outcome in each case. We observed that adenoviral and lentiviral vectors were efficient vehicles for all the cell lines, whereas Semliki Forest virus and Sindbis virus vectors yielded only a few percent of transgene -positive cells. Despite sufficient gene transfer rates ( 25 ± 45% ) in the ganciclovir ( GCV ) sensitivity experiment, only DU -145 cells were efficiently destroyed under clinically relevant GCV concentrations. This was shown to be due to low level of``bystander effect'' in PC -3 and LNCaP cells. Our data demonstrate that human prostate tumors can be good targets for adenovirus -or lentivirus -mediated HSV -TK / GCV gene therapy, but each tumor should be investigated for gene transfer rate and bystander effect to warrant a sufficient treatment result.

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“…26 ). Because VSV-G pseudotyped lentiviruses can efficiently introduce new genetic material to a variety of nondividing cells, they are potential vectors for many solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy

et al. 2001

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“…30 Conversely, a potential disadvantage is that only a fraction of cells within human tumours are actually cycling at any given time. 8 Lentiviral vectors, in contrast, are capable of infecting both dividing and nondividing cells, [10][11][12][13] although a recent report has suggested a cell cycle requirement for transduction of hepatocytes in vivo. 31 We confirmed that the Lenti-GALV, but not the lower titre C-type, stocks could infect both dividing and nondividing human tumour cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…There is a breadth of knowledge on how to target the infection and expression of retroviral vectors, 9 they are relatively lacking in immunogenicity and there is extensive knowledge of vector production and safety issues with these vectors. Moreover, the development of the lentiviral vectors has opened many new potential opportunities, [10][11][12][13] which, as yet, have not been explored for cancer gene therapy. In this respect, the ability of lentiviral vectors to infect both dividing and nondividing cells in a tumour may overcome some of the barriers to efficient gene delivery to human tumours experienced with C-type retroviral vectors, 14 where only a relatively small proportion of tumour cells may be cycling at any given time.…”

Section: Introductionmentioning

confidence: 99%

A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy

et al. 2000

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The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xen-

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“…HIV-1 based vectors have also been shown to have activity against HIV-1 itself. [4][5][6] Importantly, HIV-1 vectors especially have shown excellent utility in infecting hematopoietic stem cells. [7][8][9] Despite the appeal of certain features of HIV-1-based vectors, non-HIV-1-based lentiviral vectors that are able to infect nondividing cells might have a distinct 'psychological' advantage over HIV-1-based vectors for human gene therapy.…”

Section: Prospectsmentioning

confidence: 99%