Combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is

HSV-1 is a large DNA virus with a broad host range that can be engineered to accommodate multiple or large therapeutic transgenes (4). Although the wild-type virus may be reactivated from latency under the influence of a variety of stresses, completely replication defective viruses can be constructed that retain the ability to establish persistent quiescent genomes in neurons, but that are unable to subsequently reactivate in the nervous system. (1997) Herpesvirus capsid assembly and envelopment, in Structural Biology of Viruses (Chiu, W., Burnett, R., and Garcea, R., eds.), Oxford University Press, New York, NY, pp. The development of the infectious bacterial artificial chromosome system, a herpes simplex virus type 1-based vector that provides efficient infectious delivery and expression of bacterial artificial chromosome or P1-based artificial chromosome clone inserts, is reviewed. Liver tumors were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2) G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV- IL2), and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV-IL2). The intercellular delivery of functional p53-VP22 fusion protein is likely to prove beneficial in therapeutic strategies based on restoration of p53 function. Tumours established in mice with neuroblastoma cell lines expressing VP22-tk regressed upon administration of ganciclovir.

Although the wild-type virus may be reactivated from latency under the influence of a variety of stresses, completely replication defective viruses can be constructed that retain the ability to establish persistent quiescent genomes in neurons, but that are unable to subsequently reactivate in the nervous system. Methods: The vitreous chambers of murine eyes were infected with equivalent amounts of F or NS strains of HSV. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. A recombinant adenoviral vector encoding the HSV-TK gene was used to induce GCV sensitivity and test the potential bystander effect in established pancreatic carcinoma cell lines and patient-derived tumor material. In addition, gene transfer to overexpress endogenous antinociceptive proteins has great potential in pain management (12). Tumours established in mice with neuroblastoma cell lines expressing VP22-tk regressed upon administration of ganciclovir. (3) The viral genome translocates through the NPC.

In the HSV-GAD group, the number and amplitude of non-voiding contractions (NVCs) were significantly decreased (40-45% and 38-40%, respectively) along with an increase in voiding efficiency, compared with HSV-untreated and HSV-LacZ groups, but micturition pressure was not different among the three groups. Modified mRNA evaded recognition by the innate immune system and was less immunostimulating than dsDNA or regular mRNA. RESULTS: Forty-five (75%) of human immunodeficiency virus-infected women and 2709 (32%) controls were seropositive for herpes simplex virus-2 (p < 0.0001). We detected no changes in the morphology or the electrophysiological properties of thalamic, striatal or cortical neurons within a period of at least 2 weeks after HSV-1 amplicon injection. METHODS: A multimerized hypoxia-responsive enhancer (10 x HRE) was cloned upstream of the sFlk-1 gene (10 x HRE/sFlk-1). HSV has the potential to be a most useful tool for neuronal cell transgenesis and it is likely that important neurobiological questions will be answered using this vector system. These vectors have ICP34.5 deleted and have inactivating mutations in vmw65. The infectious properties of the herpes simplex virus type 1 (HSV-1) mutant, hrR3, with or without liposomes in the presence of neutralizing antibodies were evaluated using replication and cytotoxicity assays in vitro. Although the wild-type virus may be reactivated from latency under the influence of a variety of stresses, completely replication defective viruses can be constructed that retain the ability to establish persistent quiescent genomes in neurons, but that are unable to subsequently reactivate in the nervous system. These vectors can be prepared to high titer and purity without contamination from wild type.34, 35, 36 Delivery of the replication-defective vector to neurons innervating the site of vector delivery at the time of surgery would reduce the complications associated with systemic delivery of trophic factors, as the vector would express the neurotrophin solely within neurons that innervate the site of vector delivery. Moving walls are generally represented in years. The development of the infectious bacterial artificial chromosome system, a herpes simplex virus type 1-based vector that provides efficient infectious delivery and expression of bacterial artificial chromosome or P1-based artificial chromosome clone inserts, is reviewed. Bergami, L.M.E. To follow the spread of VP22-EGFP to other cells, transduced COS-7 cells were coplated with a number of different cell types, including brain choroid plexus cells, human endothelial cells, H9 cells, and HeLa cells. Nevertheless, to achieve an efficient intracellular delivery, further strategies to bypass the endocytotic pathway must be investigated. Similarly, the infection efficiency of an HSV1716 variant for semi-permissive human leukaemic, CD38-positive cell lines was greatly improved by an anti-CD38 scFv targeting moiety linked to gD residues 274-393, and this enhanced infectivity was abrogated specifically by an anti-CD38 monoclonal antibody.