Patent classifications
C12N2830/60
CANCER IMAGING WITH THERAPY: THERANOSTICS
Genetic constructs comprising reporter genes operably linked to cancer specific or cancer selective promoters (such as the progression elevated gene-3 (PEG-3) promoter and astrocyte elevated gene 1 (AEG-1) promoter) are provided, as are methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols, e.g. for imaging and/or treating spontaneous metastasis. Transgenic animals in which a reporter gene is linked to a cancer specific or cancer selective promoter, and which may be further genetically engineered, bred or selected to have a predisposition to develop cancer, are also provided.
ENGINEERED UBIQUITOUS CHROMATIN OPENING ELEMENTS AND USES THEREOF
Disclosed herein are polynucleic acid molecules, plasmids, vectors, compositions, methods, and kits for expressing a target protein. In some instances, also described herein are polynucleic acid molecules, plasmids, vectors, compositions, methods, and kits for enhancing the expression of a target protein.
PSMA-BASED MOLECULAR-GENETIC REPORTER SYSTEM
Methods, reporter gene constructs, and kits for using prostate-specific membrane antigen (PSMA) as an imaging reporter to image a variety of cells and tissues are provided.
REV-DEPENDENT LENTIVIRAL VACCINE PARTICLES FOR REDUCING VIRAL REBOUND AND VIRAL RESERVOIRS IN VIVO
Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from Bacillus anthracis, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.
GENETICALLY STABLE RECOMBINANT MODIFIED VACCINIA ANKARA (RMVA) VACCINES AND METHODS OF PREPARATION THEREOF
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.
A STRONG INSULATOR AND USES THEREOF IN GENE DELIVERY
A strong insulator fragment from foamy virus, which can be used to insulate expression of a transgene and reduce genotoxicity of integrating vectors comprising such. The insulator fragment can also be used in gene targeting constructs in gene editing.
ADENOVIRUS ARMED WITH BISPECIFIC T CELL ENGAGER (BITE)
An adenovirus comprising a sequence of formula (I) 5ITR-B.sub.1-B.sub.A-B.sub.2-B.sub.X-B.sub.B-B.sub.Y-B.sub.3-3ITR wherein By comprises a transgene cassette containing four transgenes, said genes encoding a FAP-BITE, CXL10, CXL9, and IFN. The disclosure also extends to a pharmaceutical composition comprising the virus, and use of the virus or formulation in treatment.
Single-vector gene construct comprising insulin and glucokinase genes
The invention relates to a viral expression construct and related viral vector and composition and to their use wherein said construct and vector comprise elements a) and b):
a) a nucleotide sequence encoding an insulin operably linked to a first promoter,
b) a nucleotide sequence encoding a glucokinase operably linked to a second promoter and said viral expression construct and related viral vector comprise at least one of elements c), d) and e):
c) the first and the second promoters are positioned in reverse orientation within the expression construct,
d) the first and the second promoters are positioned in reverse orientation within the expression construct and are located adjacent to each other and
e) the first promoter is a CMV promoter, preferably a mini CMV promoter.
GENE EXPRESSION SYSTEM USING STEALTHY RNA, AND GENE INTRODUCTION/EXPRESSION VECTOR INCLUDING SAID RNA
The present invention enables simultaneous and stable expression of a plurality of foreign genes by using a stealthy RNA gene expression system that is a complex that does not activate the innate immune mechanism and is formed from an RNA-dependent RNA polymerase, a single-strand RNA binding protein, and negative-sense single-strand RNAs including the following (1) to (8) : (1) a target RNA sequence that codes for any protein or functional RNA; (2) an RNA sequence forming a noncoding region and derived from mRNA expressed in animal cells; (3) a transcription initiation signal sequence recognized by the RNA-dependent RNA polymerase; (4) a transcription termination signal sequence recognized by the polymerase; (5) an RNA sequence containing a replication origin recognized by the polymerase; (6) an RNA sequence that codes for the polymerase and of which codons are optimized for the species from which an introduction target cell is derived; (7) an RNA sequence that codes for a protein for regulating the activity of the polymerase and of which codons are optimized for the species from which the introduction target cell is derived; and (8) an RNA sequence that codes for the single-strand RNA binding protein and of which codons are optimized for the species from which the introduction target cell is derived.
VERO CELL LINES STABLY EXPRESSING HSV ICP0 PROTEIN
Provided herein are Vero cell lines that stably express Herpes Simplex Virus (HSV) ICP0 protein. These cells have the same morphology of Vero cells, exhibit stable expression of HSV ICP0 protein, and also efficiently complement replication of HSV ICP0 deficient virus for greater than 20, 30, or even 40 cell passages.