Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

The present invention describes a virus-derived factor which when provided to cells, e.g., by transfecting the cells with RNA encoding the virus-derived factor, enhances expression of RNA encoding a peptide or protein in the cells. In particular, the virus-derived factor enhances survival of cells, in particular when transfected repetitively with RNA, and reduces an IFN response of cells to transfected RNA. Accordingly, the present invention provides methods and means for enhancing expression of RNA in cells. The cells are preferably transfected with the RNA.

Methods for identifying compounds in the treatment of muscular dystrophies, include the use of disease relevant cells derived from a patient. Compounds identified by these methods are useful in the treatment of muscular dystrophy.

[Problem] To provide a method for producing a population of genetically diverse regenerated T cells via iPS cells, and to provide said population of regenerated T cells.

[Solution] A method for producing a population of genetically diverse regenerated T cells via iPS cells, including: (1) obtaining a population of T cells that can recognize a target tissue or antigens from a population of the genetically diverse T cells; (2) reprogramming the obtained the population of T cells into iPS cells, culturing the iPS cells while maintaining genetic diversity; and (3) producing a population of the genetically diverse regenerated T cells from the iPS cells.

A binary vector and the provision of expression of a target antigen-dependent regulatory cytokine using the synNotch technology, so as to partially release the cytokine to enhance the function of T cell and reduce the non-specific toxic and side effect of the cytokine. A synthetic notch receptor is used to construct plasmid vectors to achieve local cytokine secretion. One plasmid vector uses a specific antibody as an extracellular domain for identifying a target antigen, a notch core comprises a transmembrane domain and a specific enzyme cutting site on a notch receptor, and transcription factor GAL4VP64 is used as an intracellular domain. When the target antigen is identified, the enzyme cutting site on the notch will be identified by a corresponding enzyme to hydrolyze and cut the intercellular transcription factor GAL4VP64. Another plasmid vector carries DNA identification/binding domain GAL4UAS of transcription factor GAL4 and correspondingly activates a minimal promoter of a target gene, and after being hydrolyzed and cut, GAL4VP64 will be bound to the binding domain to activate transcription of subsequent genes so as to express IL12 and secrete same out of the cell.

Provided are methods and compositions for inducing cells of the inner ear (for example, cochlear and utricular hair cells) to reenter to cell cycle and to proliferate. More particularly, the invention relates to the use of agents that increase c-myc activity and/or Notch activity for inducing cell cycle reentry and proliferation of cochlear or utricular hair cells and/or cochlear or utricular supporting cells. The methods and compositions can be used to promote the proliferation of hair cells and/or supporting cells to treat a subject at risk of, or affected with, hearing loss or a subject at risk of, or affected with vestibular dysfunction.

The present Application is related to methods and compositions for reprogramming adult somatic cells into induced pluripotent stem cells by targeting and remodeling endogenous gene loci without relying on ectopic expression of transcription factors.

To produce and/or maintain nave pluripotent stem cells capable of highly expressing genes important for maintaining an undifferentiated state, which could not be achieved by known methods for producing pluripotent stem cells. The present invention can produce nave pluripotent stem cells capable of maintaining an undifferentiated state by introducing and allowing transient expression of six genes (Oct3/4, Klf4, c-Myc, Sox2, Nanog, and Klf2) among the so-called initializing factors, and further performing culturing in a medium containing LIF, an MEK inhibitor, a GSK3 inhibitor, a cAMP production promoter, a TGF- inhibitor and a PKC inhibitor. Thus, the problem of the present invention can be solved.

The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.

A method of generating an artificial 3D tissue culture of a cancer grown in non-cancerous tissue, includes the steps of providing an aggregate of pluripotent stem cells or progenitor cells, culturing and expanding the cells in a 3D biocompatible matrix, wherein the cells are allowed to differentiate to develop the aggregate into a tissue culture of a desired size; wherein at least a portion of the cells are subjected to cancerogenesis by expressing a oncogene and/or by suppressing a tumor suppressor gene during any of the steps or in the tissue culture, and further including the step of allowing the cells with an expressed oncogene or suppressed tumor suppressor to develop into cancerous cells; drug screening methods; oncolytic virus screening methods; a 3D tissue culture; and a kit for performing the inventive methods.