Abstract: The present invention provides methods for preparing expanded tumor infiltrating lymphocytes (TILs) having reduced expression of PD-1 and TIGIT using sequential electroporation of two TALEN systems targeting PD-1 and TIGIT. Such TILs find use in therapeutic treatment regimens for cancer patients.

Abstract: The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to rules for designing highly active and specific TALE-base editors displaying improved on-target/off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE-base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.

Abstract: The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.

Abstract: A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.

Abstract: The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of genetically modified TILs with reduced expression of CISH and optionally PD-1 as described herein.

Abstract: The present invention generally relates to the field of genome engineering (gene editing), and more specifically to ex vivo gene therapy for the treatment of Activated PI3kinase Delta Syndrome type 1 (APDS1) related to PIK3CD gene. Particularly, the present invention pertains to the treatment of PIK3CD deficiency in hematopoietic stem cells (HSCs) and/or T-cells. The present invention provides means and methods for genetically modifying HSCs and/or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous PIK3CD locus, at least in the PIK3CD allele comprising at least one APDS1-associated mutation, thereby allowing the restoration of the normal cellular phenotype.

Abstract: A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.

Abstract: The present invention relates to the design of improved TALE protein fusions useful as sequence-specific genomic reagents, such as TALE-nucleases and TALE base editors, displaying higher on-target/off-target activity ratios. Its goal is to produce safer reagents to genetically modify the genomes of different types of cells, especially mammalian cells, in particular for their use in gene therapy.

Abstract: The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.

Abstract: The present invention relates to the field of genome engineering (gene editing). More specifically the invention provides with allele specific TALE-nucleases and methods to operate allele specific gene repair by homologous recombination in primary cells, such as hematopoietic stem cells, blood cells and hepatocytes. These reagents and methods can be used for the genetic treatment of inherited disease, such as sickle cell disease betathalassemia.

Abstract: A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.