Abstract: Methods are provided for the cell-based delivery of collagen VII for the treatment of Epidermolysis Bullosa and corneal erosion. The disclosure also provides a composition and a pharmaceutical composition comprises, comprise, or alternatively consist essentially of, or yet further consist of a keratinocyte sheet or a corneal cell sheet.

Abstract: Compositions and regimens useful in treating type I citrullenemia are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Argininosuccinate Synthase 1 (ASS1).

Abstract: Pichia pastoris alcohol oxidase 1 (AOX1) promoter variants include at least one of the specified modifications on wild-type Pichia pastoris AOX1 promoter (SEQ ID NO: 1). The modifications include the following: a) integration of a Cat8 transcription factor binding site (TFBS), particularly integration of SEQ ID NO: 6 or SEQ ID NO: 7 or other gene sequences that show at least 80% similarity with these sequences, at any position within nucleotides 94 to 110, 141 to 160, 312 to 330, 355 to 380, 501 to 521; 640 to 658, 674 to 693, and 1 to 840; b) integration of Aca1 or Aca2 TFBS particularly integration of SEQ ID NO: 8 or other gene sequences showing at least 80% similarity with this sequence at any position between the nucleotides 1 to 840; c) mutations specified with SEQ ID NO: 2 within nucleotides 94 to 693 and combinations thereof.

Abstract: Provided is a recombinant adeno-associated virus (rAAV) having an AAVhu68 capsid and a vector genome which comprises a nucleic acid sequence encoding a functional human arylsulfatase A (ARSA). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having metachromatic leukodystrophy, or ameliorating symptoms of metachromatic leukodystrophy, or delaying progression of metachromatic leukodystrophy via administering an effective amount of rAAV to a subject in need thereof.

Abstract: The present invention relates to particles comprising RNA, in which the RNA is associated with a cationic polymer or lipid or with both a cationic polymer and lipid, wherein the RNA comprises a cytotoxic nucleotide or cytotoxic nucleotide analog and/or the RNA is covalently attached to a cytotoxin, pharmaceutical compositions containing said particles and pharmaceutical uses of the particles and pharmaceutical compositions. The particles of the present invention are particularly useful as an immunostimulating medicament capable to block proliferation or induce death in dividing cells such as tumor cells.

Abstract: The present invention relates to a polynucleotide comprising a promoter comprising a human photoreceptor-specific promoter element, a core promoter and at least one transgene. Further, the invention provides a plasmid comprising the polynucleotide, a viral vector comprising the polynucleotide and a pharmaceutical composition comprising the polynucleotide. The invention also relates to the plasmid, the viral vector or the pharmaceutical composition for use as a medicament, in particular for use in the therapy of diseases of the retina.

Abstract: The invention relates to biotechnology, to gene therapy DNA vectors, a Escherichia coli strain JM110-NAS, a method of its production and selection of gene therapy DNA vector for targeted gene therapy. The method of a gene therapy DNA vector for targeted gene therapy includes construction of a 2408 bp vector containing a 688 bp replication origin, a 467 bp transcription terminator hGH-TA, a 137 bp regulatory region RNA-out of transposon TnlO, a 1018 bp kanamycin resistance gene, and a 68 bp poly linker. Vector cleaving by XhoI and BamHI restriction endonucleases and ligation with promoter and regulatory region, while a site containing the promoter region of a human is used for the production of the gene therapy DNA vector of interest. The kanamycin resistance gene is cleaved by SpeI restriction sites. The remaining fragment was ligated to itself. The invention allows high effective targeted gene therapy.

Abstract: The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Abstract: A material for binding to a cell culturing protein is disclosed. The material contains a bulk-modified elastomer comprising a plurality of fatty acid moieties covalently bound to the elastomer bulk, wherein the carboxylic acid groups of said moieties are available to provide said binding. Also disclosed are a fluidic device module, a cell culturing scaffold, a fluidic device, the method of synthesizing such a material and a drug testing method. With such a material, a (monolithic) fluidic device module may be manufactured in as few as a single step injection molding process.

Abstract: Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a CBLB gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

Abstract: The invention provides methods of preparing a sample of viable diseased cells obtained from a human subject for clinical testing, wherein the methods inhibit anoikis and/or anoikis in the cells while maintaining the physiological functions and genomic composition of the cells when they were in vivo. In the methods of the invention, primary cells are cultured in media comprising at least one anoikis inhibitor, preferably at least one inhibitor of an intrinsic anoikis pathway and at least one inhibitor of an extrinsic anoikis pathway, under anti-anoikis atmospheric conditions, such as greater than 2% and less than 20% oxygen. Method combining multiple culturing conditions, including surface attachment under conditions that inhibit anoikis, are also provided. Compositions and kits for use in the methods of the invention are also provided.

Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient.

Abstract: The present disclosure provides methods and compositions for the treatment of diseases and genetic disorders linked to SURF1 loss and/or misfunction. The methods and compositions of the present disclosure comprise rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for a SURF1 polypeptide.

Abstract: Methods are provided for the cell-based delivery of collagen VII for the treatment of Epidermolysis Bullosa and corneal erosion. The disclosure also provides a composition and a pharmaceutical composition comprises, comprise, or alternatively consist essentially of, or yet further consist of a keratinocyte sheet or a corneal cell sheet.

Abstract: A method and vectors for controlling blood glucose levels in a mammal are disclosed. In one embodiment, the method comprises the steps of: treating the hepatocyte cells of a patient with a first, second or third vector, wherein the first vector comprises a promoter enhancer, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase and an albumin 3?UTR and lacks an HGH intron, wherein the second vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site and an albumin 3?UTR and lacks a promoter enhancer, wherein the third vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site, an albumin 3?UTR and a promoter enhancer and observing the patient's insulin levels, wherein the patient's insulin levels are controlled.

Abstract: Methods are provided for the cell-based delivery of collagen VII for the treatment of Epidermolysis Bullosa and corneal erosion. The disclosure also provides a composition and a pharmaceutical composition comprises, comprise, or alternatively consist essentially of, or yet further consist of a keratinocyte sheet or a corneal cell sheet.

Abstract: The present invention is related to compositions and methods for the regulated and controlled expression of proteins.

Abstract: Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.

Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.