Abstract: Use of cyclosporin H (CsH) or a derivative thereof for increasing the efficiency of transduction of an isolated population of cells by a viral vector and/or increasing the efficiency of gene editing of an isolated population of cells when transduced by a viral vector.

Abstract: An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.

Abstract: Disclosed herein are methods and compositions for inactivating TCR genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.

Abstract: A product comprising two or more artificial transcription repressors (ATRs), or polynucleotides encoding therefor, selected from groups (a), (b), (c) or (d): (a) an ATR comprising a DNA-binding domain operably linked to a KRAB domain or homologue thereof; (b) an ATR comprising a DNA-binding domain operably linked to a DNMT3A, DNMT3B or DNMT1 domain or homologue thereof; (c) an ATR comprising a DNA-binding domain operably linked to a DNMT3L domain or homologue thereof; and (d) an ATR comprising a DNA-binding domain operably linked to a SETDB1 domain or homologue thereof, wherein at least two of the ATRs are selected from different groups (a), (b), (c) or (d).

Abstract: A gene vector comprising a miRNA sequence target.

Abstract: A polynucleotide comprising a nucleotide sequence encoding an epidermal growth factor receptor (EGFR) extracellular epitope operably linked to: (a) a NGFR or GMS SFR alpha signal peptide; (b) a EGFR or NGFR transmembrane domain; and/or (c) a NGFR or EGFR cytosplasmic tail.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: Disclosed herein are methods and compositions for inactivating TCR genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.

Abstract: Engineered Treg-like cells, CD4LVFOXP3 T cells, and their use in cellular therapy to promote immune tolerance are disclosed. In particular, CD4LVFOXP3 T cells are produced by transduction of CD4+ T cells with a lentiviral vector expressing FOXP3 under the control of a constitutive promoter. Transduced cells express FOXP3 at high and persistent levels and acquire immune suppressive characteristics resembling naturally occurring Treg cells.

Abstract: An interleukin which binds to IL-2 receptor (IL-2R), or a nucleotide sequence encoding therefor, wherein the interleukin or nucleotide sequence is adapted to be targeted to the liver.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: A method for selecting genome edited cells and/or for enrichment of genome edited cells in a population of cells comprising: (a) introducing into a cell or a population of cells at least one first component, at least one second component and at least one third component; and (b) selecting the genome edited cells which transiently express or transiently upregulate a nucleotide sequence encoding a selector.

Abstract: An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.

Abstract: Use of CD47 and/or C-X-C chemokine receptor type 4 (CXCR4) for increasing engraftment by haematopoietic stem C and/or progenitor cells (HSPCs).

Abstract: An agent which promotes homology directed DNA repair for use in haematopoietic stem and/or progenitor cell gene therapy, wherein said haematopoietic stem cells are gene edited. Use of an agent which promotes homology directed DNA repair, for increasing the survival and/or engraftment of gene edited haematopoietic stemand/or progenitorcells or for increasing the efficiency of gene editing of haematopoietic stem and/or progenitor cells.

Abstract: An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of CD47 on the surface of the cell.

Abstract: Use of cyclosporin H (CsH) or a derivative thereof for increasing the efficiency of transduction of an isolated population of cells by a viral vector and/or increasing the efficiency of gene editing of an isolated population of cells when transduced by a viral vector.

Abstract: Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.

Abstract: The present disclosure provides lentiviral vectors comprising codon optimized Factor VIII sequences, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of the transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FVIII expression (for example, a 100-fold improvement) at low lentiviral vector doses (e.g., 5×1010 or lower, such as 1.5×109 or lower, or 1×108 TU/kg or lower). The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia A) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a codon optimized Factor VIII nucleic acid sequence at low dosages (1×108 TU/kg or lower to 1.5×1010 TU/kg).

Abstract: An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.