This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Provided are methods for propagating mesenchymal stem cells (MSC), and particularly adipose derived stem cells, including incubating isolated cells obtained from a tissue or organ including MSC in a growth medium including an apoptosis inducing agent, under specified conditions. Further provided is an isolated cell population and kits for performing the methods.

A method for producing CD4/CD8 double-positive T cells, comprising the steps of: (1) culturing pluripotent stem cells in a medium to induce hematopoietic progenitor cells; and (2) culturing the hematopoietic progenitor cells obtained in the step (1) in a medium containing a p38 inhibitor and/or SDF-1 to induce CD4/CD8 double-positive T cells.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Compositions and methods are provided for production of cells useful in regenerative therapies.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

The subject matter described herein relates to compositions and methods for cellular rejuvenation, tissue engineering, and regenerative medicine by transient exposure of cells or tissues to synthetic, non-integrative mRNAs encoding reprogramming factors. Reprogramming factor encoding polynucleotides and corresponding polypeptides that trigger less immune response, are more stable, and/or exhibit altered activity than wild-type reprogramming factors are provided. RNA vectors expressing one or more of the improved reprogramming factor polynucleotide sequences are also provided.

This disclosure relates to methods for producing immune cells with enhanced function. More specifically, disclosed herein is a method for enhancing the function of an immune cell comprising modifying an immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. Also disclosed herein is a method comprising modifying a stem or progenitor cell capable of differentiating into an immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. Also disclosed herein are immune cells or stem cells made by the present methods, as well as the use of immune cells in therapeutic treatment.

The present application discloses a cell culture media for growth, maintenance and induction of reversion to a less mature state of a cell comprising a MUC1* activating ligand.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.