Abstract: In certain preferred embodiments, the present invention provides compositions and methods for the treatment of bone conditions associated with low bone density. In preferred embodiments, the present invention provides compositions and methods for the treatment of osteoprotegerin-responsive conditions.

Abstract: The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are compositions and methods related to components of a CRISPR complex particularly comprising a Cas ortholog enzyme.

Abstract: In one aspect the present invention is concerned with a method of cell culture, comprising the steps of (i) obtaining a stem or progenitor cell sample, (ii) culturing the stem or progenitor cell sample in media and under closed conditions appropriate to cause proliferation or differentiation of the stem or progenitor cells, wherein the media comprises a vEPO protein variant, (iii) purifying the stem or progenitor cells ex vivo. The invention relates to a method of increasing the number and survival of stem and progenitor cells in vitro and in vivo using a vEPO protein variant. The invention also relates to improved differentiation of stem and progenitor cells in vitro and in vivo using a vEPO protein variant.

Abstract: A transcription factor both necessary and sufficient for human neuroectoderm specification, Pax6, as well as applications thereof, is disclosed.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: A nanoparticle conjugate for intracellular delivery of a therapeutic agent, wherein the conjugate comprises a nanoparticle, a cationic agent and the therapeutic agent. Pharmaceutical compositions, medicaments and therapeutic uses thereof are also provided.

Abstract: The presently-disclosed subject matter includes methods of identifying an Alu RNA inhibitor, and methods and compositions for inhibiting Alu RNA. Methods and compositions can be used for the treatment of geographic atrophy and other conditions of interest.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: The present invention relates to a transfected mammalian host cell whose ability to secrete a foreign protein has been enhanced by using a foreign gene expression vector having a promoter derived from a human gene, and a method for producing the foreign protein using the host cell. A method for enhancing the production of a foreign protein to be used in a pharmaceutical protein product in a host cell such as a cultured mammalian cell is provided. A promoter derived from a human gene having a promoter activity higher than that of a cytomegalovirus (CMV) promoter in a host cell such as a cultured mammalian cell is provided.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.

Abstract: The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are compositions and methods related to components of a CRISPR complex particularly comprising a Cas ortholog enzyme.

Abstract: Recombinant proteins for siRNA delivery and a composition including same. These recombinant proteins include a p19 RNA binding protein and a target oriented peptide and can secure the stability of siRNAs from external attacks such as various degradation enzymes, have selective binding affinity to cancer cells by virtue of target-oriented peptides having various cancer cells as their target, and silence target genes by effectively delivering the siRNAs to cells and biological tissues by the release of the siRNAs to the cytoplasms after the cell penetration thereof. Therefore, they are expected to be effectively employed as siRNA delivery vehicles for siRNA therapeutic agents, cell-based drug screening compositions and research.

Abstract: A method to increase the efficiency of transduction of hematopoietic and other cells by retroviruses includes infecting the cells in the presence of fibronectin or fibronectin fragments. The fibronectin and fibronectin fragments significantly enhance retroviral-mediated gene transfer into the cells, particularly hematopoietic cells including committed progenitors and primitive hematopoietic stem cells. The invention also provides improved methods for somatic gene therapy capitalizing on enhanced gene transfer, hematopoietic cellular populations, and novel constructs for enhancing retroviral-mediated DNA transfer into cells and their use.

Abstract: Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

Abstract: The present invention relates to a composition for enhancing an immune response, an epitope having immunogenicity, screening and preparing method thereof, a antibody to peptide antigen and screening and preparing method thereof. The composition of the present invention may be effectively used for preventing or treating diverse immune-deficiency diseases such as cancer, influenza virus, hepatitis C virus and RSV (respiratory syncytial virus) by enhancing immune responses.

Abstract: The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are compositions and methods related to components of a CRISPR complex particularly comprising a Cas ortholog enzyme.

Abstract: Human pluripotent embryonic stem cells produced by somatic cell nuclear transfer as well as methods of making and using said human pluripotent embryonic stem cells are disclosed.

Abstract: The present disclosure relates to a nucleic acid assembly (NAA), comprising sensor domain and handle domain; an assembly interfaceable motif (AIM) sequence optionally along with intracellular targeting motif (ITM) sequence; and an AIM-NAA complex. It also relates to a vector comprising assembly interfaceable motif sequence optionally along with intracellular targeting motif sequence and a cell comprising the vector. Further, the instant disclosure also provides a method to obtain the nucleic acid assembly, method of intracellular targeting and kit thereof.

Abstract: The present invention relates to an eukaryotic expression vector comprising a nucleotide sequence encoding for the human long pentraxin PTX3 protein under the control of an effective promoter and a nucleotide sequence encoding for a selectable marker, recombinant human cell able to provide expression of proteins encoded by the vector and method for the production of the human long pentraxin PTX3 protein.

Abstract: The use of therapeutically active lipids for organ/tissue-specific enrichment for the treatment of inflammatory, ischemic or degenerative disorders and/or for stimulating a regeneration is arranged and developed such that the lipids are bound on application to carrier molecules for which cell-specific uptake systems in the cells of the organs and/or tissue exist. In addition, a method of producing organ/tissue-specific therapeutically active lipids for treatment of inflammatory, ischemic or degenerative disorders and/or stimulation of a regeneration, in particular for treating inflammatory liver disorders, is claimed, which is arranged and developed such that lysophosphatidylethanolamine (LysoPE) is coupled to the carboxyl group of ursodeoxycholate (UrsoDOCA) converted to an ester to give a LysoPE-DOCA compound.

Abstract: Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

Abstract: Described herein are synthetic, modified RNAs for changing the phenotype of a cell, such as expressing a polypeptide or altering the developmental potential. Accordingly, provided herein are compositions, methods, and kits comprising synthetic, modified RNAs for changing the phenotype of a cell or cells. These methods, compositions, and kits comprising synthetic, modified RNAs can be used either to express a desired protein in a cell or tissue, or to change the differentiated phenotype of a cell to that of another, desired cell type.

Abstract: Methods and means are provided for producing chimeric nucleic acid constructs capable of producing dsRNA for silencing target nucleic acid sequences of interest using recombinational cloning.

Abstract: The present invention relates to plasmid curing, and particularly to efficient and stress-free methods for displacing resident or endogenous plasmids from a host cell, such as a bacterium. The invention extends to method of displacing a plasmid comprising a post-segregational killing system from a host cell, the method comprising introducing a recombinant nucleic acid molecule into a host cell harboring a plasmid comprising a post-segregational killing (PSK) system, characterized in that the recombinant nucleic acid molecule is adapted to neutralize the toxic effects of the plasmid's post-segregational killing system, and wherein the nucleic acid molecule is also adapted to outcompete or inhibit replication of the plasmid. The invention further extends to recombinant nucleic acid molecules that can be used in this method, as well as further uses of the methods and nucleic acid molecules of the invention.

Abstract: The present invention relates to isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

Abstract: The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Abstract: The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

Abstract: The present invention is directed to a method for preparing an expression vector encoding a tailored recombinase, wherein said tailored recombinase recombines asymmetric target sites within the LTR of proviral DNA of a retrovirus inserted into the genome of a host cell and is useful as means for excising the provirus from the genome of the host cell. The present invention further relates to an in vitro-method of optimising the treatment of a retroviral infection of a subject and to the use of tailored recombinases for the preparation of pharmaceutical compositions for reducing the viral load in a subjected infected by a retrovirus.

Abstract: Disclosed herein are methods and compositions for modulating activity of CXCR4 genes, for example using zinc finger transcription factors (ZF-TFs) or zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZF-TFs or ZFNs, vectors comprising polynucleotides encoding ZF-TFs or ZFNs and cells comprising polynucleotides encoding ZF-TFs or ZFNs and/or cells comprising ZF-TF or ZFNs are also provided.

Abstract: An object of the present invention is to provide an RNAi control system using an RNA-protein interaction motif. The present invention provides an shRNA comprising: a guide strand having a sequence complementary to a target sequence; a passenger strand which forms a duplex with the guide strand; and a linker strand which links the guide strand and the passenger strand, wherein the linker strand comprises an RNP-derived protein-binding motif sequence. The present invention also provides an RNAi control system comprising: the shRNA; and an RNP-derived protein which specifically binds to a protein-binding motif sequence in the shRNA.

Abstract: Provided is a method of selecting highly safe pluripotent stem cells that do not exhibit differentiation resistance, comprising the steps of (1) inducing a pluripotent stem cell to differentiate, (2) culturing the cell under conditions for maintaining undifferentiated state, (3) detecting the generation of an undifferentiated cell by the cultivation, and comparing the finding with a control, and (4) selecting a pluripotent stem cell whose detected value is not more than a control generation value.

Abstract: The embodiments disclosed herein relate to the construction of fully-deleted Adenovirus-based gene delivery vectors packaged without helper Adenovirus, and more particularly to their use in gene therapy for gene and protein expression, vaccine development, and immunosuppressive therapy for allogeneic transplantation. In an embodiment, a method for propagating an adenoviral vector includes (a) providing an Adenovirus packaging cell line; (b) transfecting a fully-deleted Adenoviral vector construct into the cell line; and optionally (c) transfecting a packaging construct into the cell line, wherein the fully-deleted Adenoviral vector construct and optionally the packaging construct can transfect the Adenovirus packaging cell line resulting in the encapsidation of a fully-deleted Adenoviral vector independent of helper Adenovirus. In an embodiment, a target cell is transduced with the encapsidated fully-deleted Adenoviral vector for treating a condition, disease or a disorder.

Abstract: The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.

Abstract: Aspects of the present disclosure are directed to methods and compositions for the production of heterogeneous tissue from human induced pluripotent stem (hiPS) cells.

Abstract: The present invention provides a method of stimulating growth of a pancreatic islet beta cell and/or enhancing glucose stimulated insulin secretion of a pancreatic islet beta cell, comprising delivering to the cell an exogenous nucleotide sequence encoding Nkx6.1 transcription factor.

Abstract: The invention provides, inter alia, recombinase-based systems that provide for integrated logic and memory in living cells.

Abstract: Isolated polynucleotides comprising a CCKBR mini-promoters are provided. The mini-promoter may be operably linked to an expressible sequence, e.g. reporter genes, genes encoding a polypeptide of interest, regulatory RNA sequences such as miRNA, siRNA, anti-sense RNA, etc., and the like. In some embodiments a cell comprising a stable integrant of an expression vector is provided, which may be integrated in the genome of the cell. The promoter may also be provided in a vector, for example in combination with an expressible sequence. The polynucleotides find use in a method of expressing a sequence of interest, e.g. for identifying or labeling cells, monitoring or tracking the expression of cells, gene therapy, etc.

Abstract: Intact bacterially derived minicells containing functional nucleic acids or plasmids encoding functional nucleic acids can reduce, in targeted mammalian cells, drug resistance, apoptosis resistance, and neoplasticity, respectively. Methodology that employs minicells to deliver functional nucleic acids, targeting the transcripts of proteins that contribute to drug resistance or apoptosis resistance, inter alia, can be combined with chemotherapy to increase the effectiveness of the chemotherapy.

Abstract: Methods and compositions relating to the production of induced pluripotent stem cells (iPS cells) are disclosed. For example, induced pluripotent stem cells may be generated from CD34+ hematopoietic cells, such as human CD34+ blood progenitor cells, or T cells. Various iPS cell lines are also provided. In certain embodiments, the invention provides novel induced pluripotent stem cells with a genome comprising genetic rearrangement of T cell receptors.

Abstract: The present invention relates to methods of synthesizing long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, in recombinant cells such as yeast or plant cells. Also provided are recombinant cells or plants which produce long-chain polyunsaturated fatty acids. Furthermore, the present invention relates to a group of new enzymes which possess desatorase or elongase activity that can be used in methods of synthesizing long-chain polyunsaturated fatty acids.

Abstract: The invention relates to a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g.

Abstract: The present invention relates to methods for changing the state of differentiation of a eukaryotic cell, the methods comprising introducing mRNA encoding one or more reprogramming factors into a cell and maintaining the cell under conditions wherein the cell is viable and the mRNA that is introduced into the cell is expressed in sufficient amount and for sufficient time to generate a cell that exhibits a changed state of differentiation compared to the cell into which the mRNA was introduced, and compositions therefor. For example, the present invention provides mRNA molecules and methods for their use to reprogram human somatic cells into pluripotent stem cells.

Abstract: The present invention is based on the discovery that a single lentiviral vector expressing multiple individual transcription factor proteins from a single multi-cistronic mRNA can reprogram a fibroblast cell to a stem cell-like cell. These reprogrammed induced pluripotent stem (iPS) cells are pluripotent. Additions of the Cre-LoxP sequences into the single lentiviral vector facilitate excision of the vector after reprogramming in achieved. Addition of a maker gene into the single lentiviral vector facilitates detection of the presence of the vector in an iPS. The invention provides compositions and methods of producing iPS cells using a single multi-cistronic lentiviral vector.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing one or more proteins under the control of a gene expression modulation, system in the presence of activating ligand and uses for therapeutic purposes in animals. The vector may be provided to treat or prevent disease.

Abstract: Disclosed herein are compositions of transcription activator-like effectors transcription factors and methods of using said compositions for inducing gene expression of mammalian genes.

Abstract: A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain by delivering a definite concentration of recombinant neurotrophin, into a targeted region of the brain using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. Growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated is provided.