A new promoter comprising: (i) an hCMV enhancer sequence; (ii) an hCMV promoter sequence; (iii) a splice donor region; (iv) a cell-derived enhancer sequence; and (v) a splice acceptor region.

The present invention provides methods for improving the efficiency of inducing pluripotent stem cells, as well as vectors and compositions for use therein. In the induction of pluripotent stem cells which contains the step of introducing a vector that contains the KLF gene, OCT gene, and SOX gene in this order, the efficiency of pluripotent stem cell induction was successfully increased significantly by further introducing a vector that contains the KLF gene but not the OCT gene and the SOX gene. The methods of the present invention have an excellent feature in that they allow efficient induction of pluripotent stem cells under a temperature condition closer to the physiological environment, and prompt vector removal after the pluripotent stem cell induction. The present invention enables more efficient induction of pluripotent stem cells.

The present invention includes compositions and methods for multiplexed genome editing and screening in vivo. In certain aspects, the invention includes an CCAS library for multiplexed genome-scale mutagenesis.

Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.

Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.

Provision of a modified promoter derived from a xylanase promoter. A modified promoter comprising a polynucleotide of Xyn3 promoter comprising a polynucleotide that comprises at least one polynucleotide of Xyn1 promoter cis-element or a complementary strand thereof in a region corresponding to the nucleotides at position 374 to 401 of SEQ ID NO:1. The polynucleotide of Xyn3 promoter consist of the following nucleotide sequences: the nucleotide sequence represented by SEQ ID NO:1; the nucleotide sequence represented by the nucleotides at position 350 to 1084 of SEQ ID NO:1; or a nucleotide sequence that has an identity of at least 90% therewith and that comprises the sequence represented by SEQ ID NO:2 in a region corresponding to the nucleotides at position 374 to 401 of SEQ ID NO:1. The polynucleotide of Xyn1 promoter cis-element consists of the nucleotide sequence represented by SEQ ID NO:4.

The present disclosure relates to: an adipocyte-targeting non-viral gene delivery complex comprising a sh(FABP4+FABP5) dual plasmid vector; and treatment for obesity and obesity-induced metabolic syndromes by using the same and, more particularly, to a gene delivery complex comprising: an adipocyte-targeting sequence; a nine-arginine (R9) peptide; and a dual plasmid vector comprising a gene for treatment of obesity and obesity-induced metabolic syndromes, wherein the gene for treatment of obesity and obesity-induced metabolic syndromes is a base sequence inhibiting the expression of a FABP4 gene and a FABP5 gene. According to the present disclosure, in order to treat obesity-related diseases, a dual plasmid vector capable of simultaneously inhibiting the FABP4 and FABP5 genes is produced, and this vector is bound to a predetermined delivery system that specifically delivers the vector into adipocytes so as to provide a gene delivery complex. In this way, it is possible to achieve an excellent therapeutic effect on obesity which targets only adipocytes without cytotoxicity.

Herein is reported that for transient transfections the use of the human elongation factor 1 alpha promoter (with Intron A) provides for an enhanced productivity (in LC-HC-SM organization), the use of the bovine growth hormone polyA signal sequence provides for an enhanced productivity compared to use of the SV40 polyA signal sequence, the addition of the HUT to the bGH PolyA signal sequence results in an increased productivity in vectors containing the hCMV promoter and the vector organization LC(3-5)-HC-SM results in improved expression. For stable pools it is reported that pools generated with vectors containing the hEF1 promoter show an enhanced productivity in batch analysis, clones generated with vectors containing the hEF1 promoter show a reduced number of low producing clones, and clones generated with vectors containing the hEF1 promoter show a higher stability of IgG expression. For single clones it is reported that the vector organization with downstream position of selection marker (LC-HC-SM) has a positive effect on productivity of single clones and that clones generated with vectors containing the bGH polyA signal sequence and the hGT have higher productivities.

Expression vectors ideal for use in vaccinating individuals against disease based on vaccinia virus and other chordopoxviruses having high expression of recombinant genes and low expression of vector genes in target animals, and low expression of recombinant genes and high expression of vector genes in cells used for propagation.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.