Provided are method for generating αβ T cells from induced pluripotent stem cells. Also provided are genetically engineered iPSCs, αβ T cells, CAR-αβ T cells, and methods of using the same.

The present disclosure provides compositions and methods for use in genome engineering of induced pluripotent stem cells (iPSCs). Specifically, the methods and compositions described are useful for introducing transgenes into iPSCs such as pluripotent hematopoietic stem cells and/or progenitor cells (HSC/PC) using an CRISPR nuclease-based system (e.g., MAD7 nuclease-based system) and preparing immune-effector cells derived from the iPSCs.

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 at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further 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 said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

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 at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further 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 said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency.

The present invention relates to the field of stem cells. More specifically, the present invention provides compositions and methods for using optogenetics to sustain the pluripotency of stem cells. In one embodiment, a vector comprises a nucleotide sequencing encoding a fusion protein comprising the intracellular domain of fibroblast growth factor 1 receptor (FGFR1) and a photoactivatable domain.

Methods for generating clinically safe NK cells derived from non-fully differentiated stem cells and their use in treating cancer are provided. The non-fully differentiated stem cells are co-cultured with endogenous NK cells isolated from adipocyte-containing tissue to generate a high percentage of clinically safe NK cells, where anti-tumor activity of the clinically safe NK cells in vitro is similar to that of endogenous NK cells. Optimized Production of the clinically safe autologous NK cells from stem cells provides platform for treating cancer patients by applying an effective adoptive immunotherapy ranging from the early to terminal stages.

Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Disclosed herein are methods to reliably and robustly generate a pure population of airway basal cells that are capable of producing a normal mucociliary epithelium. Such basal cells may be used to treat chronic respiratory diseases, such as cystic fibrosis, chronic obstructive pulmonary disease, and asthma.

Disclosed herein are mortal pluripotent stem cells produced in vitro and compositions thereof. Disclosed herein are methods of treating a disorder or condition by utilizing the cells disclosed herein. Also disclosed herein are methods of growing cells in culture medium as well as populations of mortal pluripotent stem cells differentiated therefrom.