Abstract: The invention relates to an isolated cell having, after culturing a pluripotent stem cell (PSC) in a medium comprising a WNT agonist and an ACTIVIN antagonist, increased HOXA gene expression relative to a PSC not cultured in a medium comprising a WNT agonist and an ACTIVIN antagonist, wherein the cell with increased HOXA gene expression is capable of generating a definitive haematopoietic stem/precursor cell. The invention also relates to use of the cell for generating a definitive haematopoietic stem/precursor cell, and a method for differentiating a PSC into a definitive haematopoietic stem/precursor cell and a definitive haematopoietic stem/progenitor cell differentiated from a PSC by the method. The invention further relates to a therapeutic composition comprising a cell of the invention, and to therapeutic methods and uses of a cell of the invention.

Abstract: The invention relates to a method for producing a lymphocyte progenitor, the method comprising culturing a pluripotent stem cell (PSC)-derived CD34+ cell at an air-liquid interface (ALI). The invention also relates to a method for producing a B-cell progenitor, the method comprising co-culturing a PSC-derived CD34+ cell and a stromal cell in a medium comprising a CD117 activator and a NOTCH1 inhibitor. The invention further relates to a T-cell progenitor and a B-cell progenitor when produced by the methods of the invention and to use of the T-cell progenitor in the manufacture of T cell with defined antigen specificity, optionally a chimeric antigen receptor (CAR) T cell, and use of the B-cell progenitor in the manufacture of an antibody.

Abstract: The invention relates to a vector comprising: a 5? nucleic acid that is homologous to a genomic sequence 5? of a stop codon of a constitutively expressed gene; an exogenous nucleic acid; a 3? nucleic acid that is homologous to a genomic sequence 3? of the stop codon of the constitutively expressed gene; a translation interruption-reinitiation signal operably linked to the 5? nucleic acid and the exogenous nucleic acid, wherein the translation interruption-reinitiation signal is capable of replacing the stop codon of the constitutively expressed gene.

Abstract: The invention relates to an isolated cell having, after culturing a pluripotent stem cell (PSC) in a medium comprising a WNT agonist and an ACTIVIN antagonist, increased HOXA gene expression relative to a PSC not cultured in a medium comprising a WNT agonist and an ACTIVIN antagonist, wherein the cell with increased HOXA gene expression is capable of generating a definitive haematopoietic stem/precursor cell. The invention also relates to use of the cell for generating a definitive haematopoietic stem/precursor cell, and a method for differentiating a PSC into a definitive haematopoietic stem/precursor cell and a definitive haematopoietic stem/progenitor cell differentiated from a PSC by the method. The invention further relates to a therapeutic composition comprising a cell of the invention, and to therapeutic methods and uses of a cell of the invention.

Abstract: The invention relates to a vector comprising: a 5? nucleic acid that is homologous to a genomic sequence 5? of a stop codon of a constitutively expressed gene; an exogenous nucleic acid; a 3? nucleic acid that is homologous to a genomic sequence 3? of the stop codon of the constitutively expressed gene; a translation interruption-reinitiation signal operably linked to the 5? nucleic acid and the exogenous Targeting nucleic acid, wherein the translation interruption-reinitiation signal is capable of replacing the stop codon of the constitutively expressed gene.

Abstract: The present invention provides methods for in vitro production of clinically useful quantities of differentiated human blood cells. In various embodiments of the present invention, immortal pluripotent cells are used to produce differentiated blood cell populations using a cell production device. In a specific embodiment, the device is a sequential series of bioreactors utilizing growth media containing specific combinations of maintenance-, proliferation- or differentiation-promoting factors that maintain, expand and promote the maturation and differentiation of the desired cell types. The immortal pluripotent cells can optionally be genetically modified so as to remove histcompatibility or blood group antigens.