Provided are an oncolytic virus, a preparation method therefor, the use thereof and a medicine thereof, wherein the genome of the oncolytic virus includes the following exogenous elements: (1) a first expression cassette containing a first promoter and a first interfering RNA expression sequence; (2) a target sequence; and (3) a second expression cassette. The replication of the oncolytic virus is regulated and controlled by exogenous elements inserted into the genome sequence thereof; by means of the regulation and control by the exogenous elements, the oncolytic virus can be selectively replicated in different types of cells, and thus, second cells, that is, target cells (such as tumor cells), can be selectively killed, and first cells, that is, non-target cells (such as normal cells), are not damaged.

The present disclosure relates to one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for increasing production of a TLR3 precursor protein. Embodiments of the present disclosure can be used as a therapy or a treatment for a subject that has a condition whereby the subject's immune system is, or is likely to become, dysregulated and where the production of the TLR3 precursor protein may result in an increased production of a functional and bioavailable TLR3 protein product, which may be of therapeutic benefit.

The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

The disclosure provides a non-natural herpes simplex virus (“HSV”), compositions comprising, or alternatively consisting essentially of, or yet further consisting of the HSV, and methods of producing the HSV, or infecting a cell with the HSV. Also provided herein are methods of treating cancer or inhibiting the growth or metastasis of cancer cell in a subject in need thereof.

The present disclosure provides a bispecific single-chain antibody, recombinant oncolytic virus for expressing same and virus composition. The antibody named BiTEs-PD-L1 is a bispecific antibody capable of simultaneously binding CD3 and PD-L1 on the surfaces of tumor cells, and it can effectively activate T cells and guide T cells to kill tumor cells. The oncolytic virus oHSV2-BiTEs-PD-L1 is further developed by utilizing the BiTEs-PD-L1, it can reduce frequency and dosage of the administration. The present disclosure also confirmed several virus compositions with excellent antitumor effect.

The invention provides a method of modulating electrophysiological activity of an excitable cell. The method involves causing exogenous expression of a glycine receptor (GlyR) protein in an excitable cell of a subject. Thereafter, the excitable cell is exposed to an allosteric modulator of the GlyR protein. Modulation of the exogenous GlyR protein (an ion channel) in response to the allosteric modulator modulates the electrophysiological activity of the excitable cell. The method can be used to control pain in a subject. The invention further provides a replication-defective HSV vector comprising an expression cassette encoding a GlyR protein, stocks and pharmaceutical compositions containing such vectors, and a transgenic animal.

Synthetic promoters that are differentially modulated between certain diseased cells (e.g., cancer cells) and normal cells (e.g., non-cancer cells) are described. The synthetic promoters may be used to drive expression of gene(s) of interest in a specific cell type or during a specific cellular state. These synthetic promoters are useful, for example, for targeted expression of therapeutic molecules in diseased cells.

Oncolytic viral vectors that incorporate one or more of the following features: viral replication restriction by insertion of microRNA (miRNA) target sequences into the viral genome; disruption of oncogenic miRNA function; cancer microenvironment remodeling; and cancer cell targeting by incorporation of protease-activated antibodies into the viral particle. Such viral vectors can be used for the treatment and prevention of cancer.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.