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.

Methods of determining the suitability of a subject for treatment with a therapeutic agent are provided. Methods of providing a personalized treatment protocol based on suitability of a subject to be treated with a therapeutic agent are also provided, as are methods of treating those subjects who are suitable.

Provided are methods of producing an isolated population of T cells for adoptive cell therapy. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer, infections, and autoimmune conditions in a patient.

The present invention relates to a composition for inducing differentiation into insulin-producing cells, and a method for inducing differentiation into insulin-producing cells. By using a differentiation inducing composition according to an exemplary embodiment or a differentiation inducing method according to an exemplary embodiment, insulin-producing cells can be prepared in a short period by effectively inducing the differentiation of various types of stem cells into insulin-producing cells, and can be mass-produced in a relatively simple manner, and thus a pharmaceutical composition for preventing or treating diabetes mellitus, comprising insulin-producing cells and/or insulin produced thereby, can be provided.

Disclosed herein are nucleic acid constructs that can be used to build genetic circuits for producing antibodies comprising split toxins. Also disclosed herein are methods of producing platelets comprising the antibodies. The platelets produced by the methods disclosed herein can be used to target circulating tumor cells.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

The present disclosure provides methods and compositions for microglia replacement therapy in a subject in need thereof. In some cases, the method involves administering myeloid cells to the central nervous system of a subject. In some cases, the myeloid cells are derived from embryonic or extraembryonic tissue. In some cases, the myeloid cells are genetically modified. The genetic modification may include a colony stimulating factor 1 receptor (CSF1R) variant that is resistant to a CSF1R inhibitor, yet retains sensitivity to its ligand (e.g., CSF1, IL34).

The present invention relates to the field of medicine, specifically the field of treatment of cancer. More specifically, the invention relates to a method for the ex vivo production of a population of highly functional NK cells from CD34-positive cells, to a population of highly functional NK cells obtained and to the use of such population of highly functional NK cells for adoptive cell therapy.

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

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.