A viral gene therapy combination therapy for cancer, using a virus to deliver a gene to a human patient, where the gene expresses a polypeptide which is not native to the wild-type virus, yet which is nonetheless therapeutically useful when administered in combination with a chemotherapeutic agent.

The present disclosure provides an engineered stem cell, comprising a vector comprising a polynucleotide comprising a nucleic acid sequence of suicide gene, a nucleic acid sequence of immune checkpoint gene and a natural cytotoxicity triggering receptor or a TNF-related apoptosis-inducing ligand, wherein the stem cell is a tumor-targeting cell. The present disclosure also provides a method for treating a cancer or enhancing intratumor immunity or enhancing immunity in tumor microenvironment in a subject, comprising administering an effective amount of the engineered stem cell of the present disclosure to the subject.

The present invention relates to a composition for preventing or treating bone diseases, comprising a BMP-2-encoding gene and HSV-tk-encoding gene, and as an active ingredient a stem cell into which a dual kill switch expression vector in which an HGPRT-encoded gene is knocked out is introduced or a cell differentiated from the stem cell, wherein the bone regeneration effect is realized by a BMP-2 growth factor and at the same time, apoptosis may also be dually controlled by the dual kill switch.

Methods of treating a cancer in a patient are provided. The methods can include obtaining a tumor sample from a patient, detecting whether CCNG1 gene expression is present in the tumor sample, diagnosing the patient with a CCNG1 inhibitor-responsive cancer when the presence of CCNG1 gene expression in the tumor sample is detected, and/or administering an effective amount of a CCNG1 inhibitor to the diagnosed patient. CCNG1 inhibitors can include a viral vector having a binding peptide that is configured to bind one or more signature (SIG) elements of an invading tumor and at least one cytocidal gene. CCNG1 inhibitors including cell penetrating peptides are also provided.

A recombinant oncolytic virus with improved safety and anticancer effect and a use thereof are disclosed. The recombinant oncolytic virus is obtained by inserting an HSV-TK fragment-encoding gene into a TK gene region to delete TK of Vaccinia virus. The oncolytic virus expresses an HSV-TK fragment to phosphorylate GCV so that cancer cells infected with the oncolytic virus and their neighboring cancer cells can be killed. GCV is also involved in the suppression of viral proliferation and thus can control side effects caused by a virus even upon the administration of a high dose of the virus.

The disclosure relates to synthetic super-enhancers activated by one or more transcription factors. In particular, the present disclosure describes synthetic super-enhancers that are activated by one or more transcription factors expressed in a target cell and used to express transgenes, such as adverse payloads, upon activation of the synthetic super-enhancer by the transcription factor(s).

The present invention relates to an oncolytic virus and the use thereof, specifically, an oncolytic virus having suppressed thymidine kinase (TK) gene expression and comprising genes encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and a complement regulatory protein; and the use of such an oncolytic virus. The oncolytic virus of the present invention maintains its efficacy even when administered intravenously, and thus, it may also be applied to the treatment of various solid cancers and metastatic cancers in addition to superficial solid cancers. In addition, the oncolytic virus of the present invention acquires resistance to complement attack by expressing a complement regulatory protein on the surface of the virus, and thus, it is stable in the blood, and it maintains stable oncolytic activity when intravenous injection, and thus, it may reduce effective viral dosage to minimize the side effects of anti-cancer drugs.

Provided herein are genetically engineered mammalian (e.g., human) cells that express one or more transgenes at a sustained expression level. Also provided are methods of making and using the cells.

Disclosed is a gene therapy vector in which the occurrence of recombination is minimized. In order to minimize the occurrence of recombination, which is a major problem in the production and infection of a retroviral vector virus that continuously expresses a therapeutic gene during virus replication, a cleaved MCMV promoter was prepared by cutting the MCMV promoter on the basis of a repeat sequence, and the cleaved MCMV promoter was introduced to prepare a vector. It was confirmed that the vector having the cleaved MCMV promoter incorporated therein does not cause recombinations even after being incubated multiple times, and shows a continuous expression of the therapeutic protein, and in cells transfected with the virus containing the vector, cell death effectively occurs when a prodrug is administered thereto. Accordingly, the vector with minimized recombination occurrence of the present invention can be advantageously used for the treatment of cancer.

Nucleic acid sequences encoding improved Herpes Simplex Virus Thymidine Kinases are provided, including their use in diagnostic and therapeutic applications. The thymidine kinases may be mutated using conservative mutations, non-conservative mutations, or both. Also provided are gene therapeutic systems, including viral and retroviral particles.