Retroviral vector-mediated expression of plasminogen activators (PAs) from endothelial cells (ECs) has been proposed as a potential therapeutic approach for intravascular thrombosis. To define the potential for gene transfer to increase fibrinolytic activity in a primate system, baboon ECs were transduced with retroviral vectors expressing wild-type and glycosylphosphatidylinositol-anchored uro...

Suicide cancer gene therapy with retroviral vector-producing cells was in the way of an adjuvant to the surgical resection of recurrent glioblastoma, although any benefit appeared to be marginal. It is likely that this therapeutic approach may have better outcomes if the vectors and transgenes are delivered more efficiently to the tumor cells. We have shown previously that tumor cells engineere...

Vectors for gene transfer and gene therapy were developed which combine the advantages of the integrase and recombinase systems. This was achieved by inserting two loxP sites for specific DNA excision into an MESV based retroviral vector. We show that this 'retroviral lox system' allows the infection of cells and the expression of transferred genes. In addition, we constructed an efficient retr...

Normal mRNA polyadenylation signals are composed of an AAUAAA motif and G/U box spaced 20 to 30 bp apart. If this spacing is increased further, then polyadenylation is disrupted. Previously it has been demonstrated that insertion of an intron will similarly disrupt this signal even though such introns are removed during a nuclear splicing reaction (X. Liu and J. Mertz, Nucleic Acids Res. 21:525...

PURPOSE To determine whether human retinal pigment epithelium (RPE) can be modified by retroviral-mediated gene transfer and to monitor the human RPE cells in the subretinal space of living rabbits with scanning laser ophthalmoscopy (SLO). METHODS Cultured human fetal retinal pigment epithelium (HFRPE) was exposed to green fluorescent protein (GFP)-transducing retroviral vectors, Moloney muri...

The generation of retroviral vectors that infect specific cell types through recognition of cell surface antigens is a promising and effective approach to targeted gene therapy of cancer. Carcinoembryonic antigen (CEA), a highly characterized, cell surface glycoprotein overexpressed by various tumor cells, provides a specific tool for tumor tissue-specific targeting by retroviral vectors. The c...

The DNA-breaking and -joining steps initiating retroviral integration are well understood, but the later steps, thought to be carried out by cellular DNA repair enzymes, have not been fully characterized. Poly(ADP-ribose) polymerase 1 (PARP-1) has been proposed to play a role late during retroviral integration, because infection by human immunodeficiency virus (HIV)-based vectors was reported t...

Recombinant retroviral vectors represent an attractive means of transferring genes into the liver because they integrate in the host cell genome and result in permanent gene expression. However, efficient gene transfer is limited by the requirement of active cell division for integration. Surgical partial hepatectomy has been the traditional method of inducing hepatocellular proliferation, but ...

While using various human complementary DNA (cDNA) sequences in the context of the murine leukemia virus (MLV)-based retroviral vector, it was found that a retroviral vector containing some human cDNA sequences produces unusually low viral titer. One of those sequences is that for the human IL-1 receptor antagonist protein (IL1RN). The RNA analysis showed that a cryptic splice acceptor sequence...

Genetically modified cells of haematopoietic and lymphocytic lineages could provide potentially curative treatments for a wide range of inherited and acquired diseases. However, this application is limited in mouse models by the low efficiency of lentiviral vectors. To facilitate the rapid production of high-titre helper-free retroviral vectors for enhanced gene delivery, multiple modifications...