30 results about "Early response gene" patented technology

The present invention relates to an avirulent, oncolytic herpes simplex virus modified from a wild-type herpes simplex virus so that both γ134.5 genes of the virus have been deleted and each replaced with an interferon-resistance gene that is expressed as an immediate-early gene. The present invention also relates to a pharmaceutical composition that includes the modified herpes simplex virus of the present invention and a pharmaceutically acceptable vehicle for in situ administration to tumor cells. Also provided in the present invention are methods for killing tumor cells in a subject and for immunizing a subject against an infectious disease, cancer, or an autoimmune disease that involve administering to a subject the modified avirulent, oncolytic herpes simplex virus of the present invention.

A vaccine comprising an immunologically effective amount of recombinant modified vaccinia Ankara (rMVA) virus which is genetically stable after serial passage and produced by a) constructing a transfer plasmid vector comprising a modified H5 (mH5) promoter operably linked to a DNA sequence encoding a heterologous foreign protein antigen, wherein the expression of said DNA sequence is under the control of the mH5 promoter; b) generating rMVA virus by transfecting one or more plasmid vectors obtained from step a) into wild type MVA virus; c) identifying rMVA virus expressing one or more heterologous foreign protein antigens using one or more selection methods for serial passage; d) conducting serial passage; e) expanding an rMVA virus strain identified by step d); and f) purifying the rMVA viruses from step e) to form the vaccine. One embodiment is directed to a fusion cytomegalovirus (CMV) protein antigen comprising a nucleotide sequence encoding two or more antigenic portions of Immediate-Early Gene-1 or Immediate-Early Gene-2 (IEfusion), wherein the antigenic portions elicit an immune response when expressed by a vaccine.

Use of a replication incompetent herpes virus capable of delivering a gene to multiple connected sites within the nervous system, which virus comprises: (a) a mutation which prevents or reduces the expression of at least two immediate early genes; and (b) a heterologous gene operably linked to a promoter active during herpes virus latency; in the manufacture of a medicament for the treatment of a central nervous system disorder, a method of determining whether a gene has an effect on a phenotype associated with a central nervous system disorder and in a method of treatment of a disorder of the central nervous system are described.

Disclosed herein are isolated promoter-regulatory regions from a newly identified WSSV immediate early (IE) gene, ie1 (immediate early gene #1), which exhibit promoter activity to drive the transcription of a target gene in non-native host cells. The isolated promoter-regulatory regions can be used in the construction of a variety of recombinant expression vectors for transforming a broad spectrum of host cells.

Various genes of herpes virus of turkeys (HVT), Marek's disease virus (MDV) and infectious laryngotracheitis virus (ILTV) have been identified as non-essential regions (and candidates for insertion sites for foreign genes) and / or as antigen-encoding regions. The former include the HVT homologue of the HSV (herpes simplex virus) gC gene, the TK (thymidine kinase) region of MDV or ILTV, ORF3 of ILTV (as defined herein), the ribonucleotide reductase (large subunit) gene of ILTV, MDV or HVT and the ribonucleotide reductase (small subunit) gene of MDV. The antigen-encoding regions include the HVT homologues of the HSV gB, gC and gH genes, the ILTV homologue of HSV gB, ORF2 of ILTV, and the HVT homologue of the HSV-1 immediate early genes IE-175 and IE-68. Manipulation of these genes allows vaccines to be prepared comprising attenuated virus or virus carrying heterologous antigen-encoding sequences.

A recombinant herpes simplex virus type-1 (HSV-1) has been constructed that carries a deletion of one of the two viral γ1 34.5 genes and other immediate early genes, which render the virus able to selectively replicate in cancer cells but not efficiently replicate in normal cells, and in which specific mutations have been introduced to enable the virus to spread among cancer cells by virus-induced fusion. Specifically, syncytial mutations have been introduced in the genes coding for glycoprotein B and glycoprotein K of the virus, enabling high replication and spread of the virus in cancer cells in the presence of substantially lower amounts of γ1 34.5 protein, which is required for optimum infectious virus produced and virus-induced cell fusion. These altered viruses or the isolated bacterial chromosomes could be used to treat various cancers including breast, liver, colon, and other tissues.

Disclosed is an enhancer for a viral promoter such as a promoter that can induce expression selectively and strongly in immunocompetent cells (e.g., lymphocytes) or blood cells. It is found unexpectedly that an intron has the above-mentioned enhancer activity. Thus, it is found that an enhancer for a promoter, which comprises an intron sequence for a major immediate early gene (MIE) of human herpes virus-6 (HHV-6) (particularly HHV-6B) or a fragment of the intron sequence, has a potent promoter activity.

A method is provided for identifying a compound which affects the formation of AMPA receptors into aggregates. A method is also provided for identifying a compound which affects the formation of synaptic connections. A method is provided for identifying a compound that modulates immediate early gene expression. A method is further provided for increasing the number of excretory synapses of a neuron, including introducing into the neuron a polynucleotide sequence encoding a Narp operatively linked to a promoter, or a Narp polypeptide, thereby increasing the number of excretory synapses of the neuron. A method is provided for treating a subject with a disorder associated with a decrease in a function or expression of Narp, including administering to the subject a therapeutically effective amount of a compound that augments Narp function or expression. A method is provided for treating a subject with a disorder associated with an increase in a function or expression of Narp, including administering to the subject a therapeutically effective of a compound that inhibits Narp function or expression. A method is provided for treating a patient having or at risk of having a disorder associated with decreased Narp expression. The method includes introducing into a cell of a patient having a disorder associated with decreased Narp expression or function a polynucleotide sequence encoding a Narp polypeptide operatively linked to a promoter. A method is provided for treating a subject having a deficiency in a neuron's immediate early gene responsiveness to a stimulus. The method includes administering a nucleic acid encoding a Narp polypeptide to said subject, wherein the administration results in amelioration of the deficiency.

The invention discloses a main cis-acting element of a shrimp white spot syndrome virus (WSSV) iel promoter and a transcription factor combined with the same and application. In the invention, by starting from transcriptional regulation of WSSV iel and carrying out structural and functional analysis on the promoter of the WSSV iel through deletion and mutation, a 12-bp DNA is found to be the maincis-acting element of the WSSV iel and is a crucial factor for the high expression of the iel. In the invention, a DNA affinity chromatography method is used for purifying a protein combined with a DNA segment from a nucleus protein Sf9, the protein is identified to be PHB2 (Poly-Beta-Hydroxybutyrate 2) through biological mass spectrometry, and the interaction between the protein and the DNA segment is proved to be specific by an electrophoretic mobility shift assay. Experiment results prove that PHB2 serves as a transcription factor and is specifically combined with a 12-bp DNA sequence of the iel promoter to start WSSV immediate early gene transcription so as to further regulate the replication of the WSSV, and can be used as an effective action target of medicaments for screening medicaments for resisting the shrimp WSSV.

The present invention provides a method of determining if a tumor cell is susceptible to killing by a chemotherapeutic agent, comprising: (a) providing a tumor cell; (b) infecting said tumor cell with a herpes simplex virus or a herpes simplex virus defective in an immediate early gene selected from the group consisting of ICP27, ICP4, and ICP22; and (c) determining the presence of apoptotic killing of said tumor cell, wherein the presence of apoptotic killing is indicative of susceptibility to said chemotherapeutic agent. Chemotherapeutic agent may include doxorubicin, etoposide, paclitaxel, cisplatin, or 5-fluorouracil. The present invention also provides a herpes simplex virus promoter construct having a lacZ gene to assess tumor resistance to chemotherapeutic agents.