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.

The invention relates to recombinant VSV viruses and viral vectors which produce a glycoprotein GP of the lymphocyte choriomeningitis virus (LCMV) instead of the G protein of the VSV, to virus producing cells which produce LCMV-GP-pseudotyped VSV virions, and to the use of said vectors and cells in the therapy of solid tumors, especially brain tumors.

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.

Provided herein are methods and compositions for a suicide gene approach comprising an expression vector comprising a cell cycle-dependent promoter driving the expression of a suicide gene. Also provided herein are methods to render proliferative cells sensitive to a prodrug after transplantation but avoids expression of the suicide gene in post-mitotic cells, such as neurons.

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.

Methods are provided for the ex vivo reprogramming of adult mammalian cells, wherein the genes used in reprogramming the adult cells are expressed with heterologous promoters that increase expression of associated genes while the cell is in a fetal or adult non-regenerative state, but down-regulated the expression of genes once cells reach a regenerative state and before the cells are reprogrammed to pluripotency. In addition, heterologous promoters uniquely expressing genes when cells are in an embryonic (pre-fetal state) are used to increase expression of toxic gene products in cancer cells.

The invention relates to recombinant VSV viruses and viral vectors which produce a glycoprotein GP of the lymphocyte choriomeningitis virus (LCMV) instead of the G protein of the VSV, to virus producing cells which produce LCMV-GP-pseudotyped VSV virions, and to the use of said vectors and cells in the therapy of solid tumors, especially brain tumors.

Modified macrophage immune cells are provided for treatment of cancer and other diseases.

The present invention provides a vector system in which a MuLV-Gag gene, a MuLV-Pol gene, and a GaLV-Env gene are expressed in two separate vectors. The vector system is capable of inserting a therapeutic gene to these two separate vectors, and in this raged, the size of an inserted gene is not limited and a variety of foreign therapeutic genes may be inserted to the vectors. Accordingly, the foreign therapeutic gene may be delivered in a safe and efficient manner to desired tissue of cells of aberrant proliferation. Therefore, the vector system is applicable in a composition for delivering a gene targeting the aberrantly dividing cells of aberrant proliferation, wherein the composition includes a retrovirus produced by cell line transfection. The vector system is also applicable in a composition for preventing or treating a disease caused by cells of aberrant proliferation of, such as cancer cells.

The invention relates to recombinant VSV viruses and viral vectors which produce a glycoprotein GP of the lymphocyte choriomeningitis virus (LCMV) instead of the G protein of the VSV, to virus producing cells which produce LCMV-GP-pseudotyped VSV virions, and to the use of said vectors and cells in the therapy of solid tumors, especially brain tumors.