Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. 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 utilizing the CRISPR-Cas system.

Abstract: The present invention relates to methods of host cell transduction utilising ecotropic retroviral vector particles. The retroviral vector particle may comprise an envelope of Friend murine leukaemia virus, in particular the envelope encoded by molecular clone PVC-211 and the host cell may be engineered to recombinantly express the Rec1 receptor. The retroviral vector particles and methods of the invention can be used to introduce expressible polynucleotide sequences of interest into host cells with high efficiency. This results in protein production methods with higher yield (mg/L) and a reduction in manufacturing costs that could be used in a range of applications including for example, the production of therapeutic proteins, vaccines and antibodies.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Disclosed are improved recombinant adeno-associated viral (rAAV) vectors having mutations in one or more capsid proteins. Exemplary vectors are provided that have altered affinity for heparin or heparin sulfate, as well as vectors, expression systems, and rAAV virions that lack functional VP2 protein expression, but are nevertheless, fully virulent. Also provided by the invention are rAAV vector-based compositions, virus particles, host cells, and pharmaceutical formulations that comprise them useful in the expression of selected therapeutic proteins, polypeptides, peptides, antisense oligonucleotides and/or ribozymes in selected mammals, including organs, tissues, and human host cells.

Abstract: The present invention pertains to vectors for regulating gene expression having at least one gene expressing cassette and at least one gene suppressing cassette, wherein the gene expression cassette encodes a polypeptide of interest, and wherein the gene suppressing cassette encodes a short interfering RNA (siRNA) molecule that reduces expression of a target gene by RNA interference. The present invention further includes vectors that contain suppressor cassettes in conjunction with cassettes upregulating gene expression regulated by either a constitutive promoter, such as a general CMV promoter, or a tissue specific promoter. The present invention further includes vectors that contain Dengue virus gene suppression cassettes. The present invention further includes pharmaceutical compositions containing such vectors, methods of modulating the expression of genes in a host using such vectors, and method of producing such vectors.

Abstract: The present invention addresses the problems of providing a method for proliferating cardiomyocytes using a miRNA that promotes the proliferation of cardiomyocytes, a vector for use in the treatment of heart disease, a pharmaceutical composition for treating heart disease, and so forth. The present invention provides a method for proliferating cardiomyocytes using a miRNA having the cardiomyocyte proliferation promoting action, a vector for use in the treatment of heart disease that comprises said miRNA, a pharmaceutical composition for treating heart disease that comprises said vector, and so forth. A particularly preferred miRNA is one that is selected from the group consisting of mature miRNAs, i.e., miR-148a, miR-148b, miR-152, and miR-373, and precursors of said miRNAs, as well as variants and analogs thereof.

Abstract: The present invention addresses the problems of providing a method for proliferating cardiomyocytes using a miRNA that promotes the proliferation of cardiomyocytes, a vector for use in the treatment of heart disease, a pharmaceutical composition for treating heart disease, and so forth. The present invention provides a method for proliferating cardiomyocytes using a miRNA having the cardiomyocyte proliferation promoting action, a vector for use in the treatment of heart disease that comprises said miRNA, a pharmaceutical composition for treating heart disease that comprises said vector, and so forth. A particularly preferred miRNA is one that is selected from the group consisting of mature miRNAs, i.e., miR-148a, miR-148b, miR-152, and miR-373, and precursors of said miRNAs, as well as variants and analogs thereof.

Abstract: The subject invention pertains to the use of fractalkine (FKN, CX3CL1) and its receptor CX3CR1 for treatment of neuroinflammation and/or neurodegeneration. In one embodiment, the present invention provides a method for treatment of neuroinflammation and/or neurodegenerative diseases, comprising: administering, to cells of a subject in need of such treatment, an adeno-associated virus that comprises a functional fractalkine gene operably linked to transcriptional control elements. In one embodiment, the subject invention is used to treat or ameliorate Parkinson's disease. The present invention can also be used to treat or ameliorate neuroinflammatory and/or neurodegenerative diseases including, but not limited to, Alzheimer's disease, epilepsy, aging, and traumatic brain injury.

Abstract: The present invention provides duplexed parvovirus vector genomes that are capable under appropriate conditions of forming a double-stranded molecule by intrastrand base-pairing. Also provided are duplexed parvovirus particles comprising the vector genome. Further disclosed are templates and methods for producing the duplexed vector genomes and duplexed parvovirus particles of the invention. Methods of administering these reagents to a cell or subject are also described. Preferably, the parvovirus capsid is an AAV capsid. It is further preferred that the vector genome comprises AAV terminal repeat sequences.

Abstract: The present invention relates to a method for increasing the efficiency of inducing pluripotent stem cells by utilizing genes Jhdm1a that modify histone. By utilizing Jhdm1a, and a stem cell inducing factor, the present invention increases the efficiency of inducing pluripotent stem cells and increases the quality of induced pluripotent stem cells. The stem cell inducing factor is a combination of Oct4 and Klf4, or a combination of Sox2, Oct4, and Klf4, or a combination of Oct4 and Sox2, and Oct4 alone. The method further comprises exposing the cells to vitamin C, which further increases the efficiency of inducing pluripotent stem cells as compared with the case where no vitamin C is used. By using less stem cell reducing factors, the method of the present invention reduces the potential carcinogenicity, obtains a high inducing efficiency, and provides high-quality induced pluripotent stem cells capable of germ-line transmission.

Abstract: This invention relates to modified bacteriophage useful for the delivery of macromolecular biopolymers and nanoparticles to target cells, e.g., disease cells, and their use in cell-selective identification and imaging, as well as the treatment and prevention of diseases and other medical conditions.

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: Systems, constructs, and methods for reprogramming cells are provided. In one aspect, for example, a transformation construct for generating iPS cells can include an expression vector having a plurality of reprogramming factors, each reprogramming factor being under control of a separate promoter.

Abstract: The present disclosure relates to recombinant adeno-associated virus (AAV) vector serotype, wherein the capsid protein of AAV serotypes is mutated at single or multiple sites. The disclosure further relates to an improved transduction efficiency of these mutant AAV serotypes. The AAV serotypes disclosed are AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10. The instant disclosure relates to nucleotide sequences, recombinant vector, methods and kit thereof.

Abstract: The present invention provides methods for producing a minus-strand RNA viral vector, which comprise using a promoter comprising a cytomegalovirus enhancer and a chicken ?-actin promoter, to induce the transcription of the genome RNA of a minus-strand RNA viral vector and the expression of minus-strand RNA viral proteins that form a ribonucleoprotein with the genome RNA. The methods of the present invention enable high efficiency production of highly safe minus-strand RNA viral vectors. The methods of the present invention are particularly useful for producing minus-strand RNA viral vectors that are deficient in envelope-constituting protein genes.

Abstract: Substantially avirulent forms of atypical porcine reproductive and respiratory syndrome (PRRS) virus and corresponding vaccines are provided which result from cell culture passaging of virulent forms of PRRS. The resultant avirulent atypical PRRS virus is useful as a vaccine in that PRRS specific antibody response is elicited by inoculation of host animals, thereby conferring effective immunity against both previously known strains of PRRS virus and newly isolated atypical PRRS virus strains. The preferred passaging technique ensures that the virus remains in a logarithmic growth phase substantially throughout the process, which minimizes the time required to achieve attenuation. The present invention also provides diagnostic testing methods which can differentiate between animals infected with field strains and attenuated strains of PRRSV.

Abstract: Provided is a method of treating cancer in a subject by inhibiting expression of PAX2. An example of a cancer treated by the present method is prostate cancer. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.

Abstract: The presently described technology relates to the modulation of specific immune responses to create a protective immunity in the treatment of autoimmune diseases and diseases requiring the transplantation of tissue. In particular, the present technology relates to the suppression of immune responses in a targeted fashion, by increasing the functional concentration of the CEACAM1 protein in a target tissue to create a localized protective immunity for the treatment of autoimmune diseases and diseases requiring the transplantation of tissue.

Abstract: An expression cassette, wherein said expression cassette comprises: (a) an ie 1 promoter from white spot syndrome virus or a variant thereof; (b) a nucleic acid sequence encoding an N-terminal gp64 signal peptide or variant thereof, a nucleic acid sequence encoding an antigenic peptide, a nucleic acid encoding a transmembrane region, and a nucleic acid encoding a gp64 cytoplasmic region or variant thereof; in which the promoter is operably linked to the nucleic acid sequence.

Abstract: The present invention relates to the insertion of a promoter sequence from an MHC class I gene promoter into a lentiviral vector in order to direct the transcription of a transgene, which preferably encodes an immunogenic polypeptide to be expressed in a mammalian cell host, preferably APC (DCs). The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.

Abstract: The present invention discloses novel influenza virus-like particles (VLPs) that contain chimeric proteins or influenza membrane proteins. The chimeric proteins are derived from fragments of influenza membrane proteins fused to heterologous proteins. The invention includes antigenic formulations and vaccines comprising VLPs of the invention as well as methods of making and administering VLPs to vertebrates, including methods of inducing immunity to infections, such as influenza.

Abstract: Various aspects of the invention provide for capsids, parvovirus capsids, hybrid parvovirus capsids, parvovirus vectors, hybrid parvovirus vectors, hybrid parvovirus particles and parvovirus particles containing polypeptides in which the sequence YCDGFYACYMDV (SEQ ID NO: 3) has been substituted into the VP2 loop of the B19 capsid protein. Polypeptides in which the sequence YCDGFYACYMDV (SEQ ID NO: 3) has been substituted into the VP2 loop of the B19 capsid protein are also provided (e.g., SEQ ID NO: 2). Other aspects of the invention provide capsids, parvovirus capsids, hybrid parvovirus capsids, parvovirus vectors, hybrid parvovirus vectors, hybrid parvovirus particles and parvovirus particles containing a polypeptide comprising SEQ ID NO: 2. Also provided in various aspects of the invention are pharmaceutical compositions and methods of delivering therapeutic agents and/or reporter peptides/proteins to target cells.

Abstract: Compositions and methods comprising bacteriophages are provided. In particular, the present invention includes novel and customized T4 bacteriophages uniquely designed for effective antigen and foreign particle presentation. The present invention also provides in vitro methods for the making of customized T4 bacteriophages. The compositions and methods of the present invention may be used for effective vaccine delivery systems.

Abstract: The present invention provides methods of transcytosing barrier epithelial cells using adeno-associated virus-4 (AAV4), adeno-associated virus-5 (AAV5), adeno-associated virus-7 (AAV7), bovine adeno-associated virus (BAAV), and vectors and particles derived therefrom. In addition, the present invention provides methods of delivering a nucleic acid across the barrier epithelia using the AAV4, AAV5, AAV7, and BAAV vectors and particles.

Abstract: The present invention relates to methods of host cell transduction utilizing ecotropic retroviral vector particles. The retroviral vector particle may comprise an envelope of Friend murine leukaemia virus, in particular the envelope encoded by molecular clone PVC-211 and the host cell may be engineered to recombinantly express the Reel receptor. The retroviral vector particles and methods of the invention can be used to introduce expressible polynucleotide sequences of interest into host cells with high efficiency. This results in protein production methods with higher yield (mg/L) and a reduction in manufacturing costs that could be used in a range of applications including for example, the production of therapeutic proteins, vaccines and antibodies.

Abstract: The present invention relates to an infectious particle having a surface displaying a ligand binding to a CD4 receptor for selectively infecting dividing CD4+ cells, said particle comprising: (a) one or more structural proteins, and (b) a vector containing a gene of interest functional in a CD4+ cell, said gene of interest encoding a Forkhead box protein 3 or a protein inducing expression of Forkhead box protein 3 in the CD4+ cell.

Abstract: The present invention provides AAV capsid proteins, virus capsids comprising said capsid proteins and virus vectors comprising said capsid proteins, wherein the AAV capsid proteins have one or more mutations, wherein the mutation(s) result in a phenotype of decreased liver transduction and/or reduced glycan binding affinity as compared to a control. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject.

Abstract: This application relates to a method for converting somatic cells to Neural Stem Cells (NSCs). Moreover this application relates to a method for converting human fibroblasts, keratinocytes or adipocytes to neural stem cells based on linked steps of genes transduction and chemically defined medium induction.

Abstract: The present invention provides methods of generating a neuronal cell from a differentiated non-neuronal cell by increasing the amount of a miR-124 microRNA, a MYT1L transcription factor, and a BRN2 transcription factor in the differentiated non-neuronal cell.

Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using novel capsid-protein-mutated rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more symptoms of disease or abnormal conditions via in situ and/or ex vivo mammalian gene therapy methods. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.

Abstract: It is intended to provide a virus vector by which an exogenous nucleotide sequence can be inserted and easily transferred into a mammalian host cell and a gene encoded by the exogenous nucleotide sequence can be expressed in the host cell, and which has a low risk of pathogenicity and is appropriately usable in gene therapy of mammals. Namely, a recombinant vector originating in HHV-6 which has an exogenous nucleotide sequence in a portion corresponding to at least one region selected from the group consisting of U2, U3, U4, U5, U6, U7, U8, U24, and U25 regions of HHV-6; or a recombinant vector originating in HHV-7 which has an exogenous nucleotide sequence in a portion corresponding to at least one region selected from the group consisting of U2, U3, U4, U7, U8, U24, U24a, and U25 regions of HHV-7.

Abstract: The present invention relates to a composition comprising colostrum and at least one agent selected from the group of hydrocolloids, wherein said colostrum and at least one agent are bioconjugated. The bioconjugated composition has improved properties compared to colstrum compositions that are not bioconjugated with a hydrocolloid agent. The composition may be used in a variety of settings, for example for topical application for treating skin diseases and skin conditions. The present invention thus also relates to use of the composition and to a method for the preparation of the composition.

Abstract: Methods for producing new neurons in the brain in vivo are provided according to aspects of the present invention which include introducing NeuroD1 into a glial cell, particularly into a reactive astrocyte or NG2 cell, thereby “converting” the reactive glial cell to a neuron. Methods of producing a neuronal phenotype in a glial cell are provided according to aspects of the present invention which include expressing exogenous NeuroD1 in the glial cell, wherein expressing exogenous NeuroD1 includes delivering an expression vector, such as a viral expression vector, including a nucleic acid encoding the exogenous NeuroD1 to the glial cell.

Abstract: The present invention relates to a vector particle for transferring biological material into cells, wherein said vector particle comprises at least: a first protein which comprises the transmembrane and extracellular domains of the feline endogenous RD114 virus envelope glycoprotein, and a second protein which comprises a ligand of the c-Kit receptor.

Abstract: The present invention relates to viral vectors that are capable of delivering a heterologous gene to the retina and in particular delivering RLBP1 to RPE and Müller cells of the retina. The invention also relates nucleic acids useful for producing viral vectors, compositions comprising the viral vectors and uses of the compositions and viral vectors. The invention also relates to methods of delivering and/or expressing a heterologous gene to the retina, improving the rate of dark adaption in a subject and treating RLBP1-associated retinal dystrophy.

Abstract: Stem-cell derived human neuronal models that mimic human Alzheimer's disease, including hereditary and sporadic Alzheimer's disease, comprising neural stem cells derived from human induced pluripotent stem cells. Also provided are purified human neurons developed from the neural stem cells that carry genomes from the Alzheimer's disease patients. The human neuronal models are neuronal models for hereditary and sporadic Alzheimer's disease, and are suitable for measurement of key behaviors of the Alzheimer's disease, providing further diagnostic tools for the development of sporadic Alzheimer's disease, and assisting in drug testing for the therapeutic treatment of Alzheimer's disease.

Abstract: A method for promoting conversion of cells into cardiomyocytic tissue is carried out by contacting fibrotic tissue (e.g., scar tissue) with a microRNA oligonucleotide or combination of microRNA oligonucleotides. The methods lead to direct reprogramming of fibroblasts to cardiomyocytes or cardiomyoblasts.

Abstract: Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles.

Abstract: The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells.

Abstract: A lipid particle can include a cationic lipid. The cationic lipid can include one or more hydrophobic tails, which can include one or more sites of unsaturation. The sites of unsaturation can include cycloalkyl groups, e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups. The lipid particle is suitable for delivering an active agent.

Abstract: The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to said vectors for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing CD40L in a cell and increasing tumor specific immune response and apoptosis in a subject, as well to uses of the oncolytic adenoviral vector of the invention for producing CD40L in a cell and increasing tumor specific immune response and apoptosis, while decreasing tumor-associated immunosuppression, in a subject.

Abstract: The present invention provides trans-complementation systems for expressing gene products in plants. In general, the invention provides systems including a carrier vector and a producer vector, both based on plant viruses. The producer vector is defective for at least one function needed for successful systemic infection of a plant, e.g., replication, cell-to-cell movement, or long distance movement. The carrier vector supplies the missing function in trans. Certain producer vectors lack a functional coat protein coding sequence, in which case the corresponding producer vector supplies coat protein in trans. The invention also provides novel plant viral vectors and methods of use, e.g., to produce polypeptides or active RNAs in plants.

Abstract: A method for converting animal cells into brown adipose tissue cells is provided that includes transforming the animal cells using an expression vector. The expression vector includes a nucleotide sequence encoding HB-EGF operatively linked to a promoter and a nucleotide sequence encoding ADAM 12 operatively linked to a promoter. Converting animal cells to brown adipose tissue cells can be used to treat obesity or to treat cancer by converting target cells to brown adipose tissue cells.

Abstract: The present invention provides methods of generating a mammalian cell that is homozygous at a locus of interest, as well as cells made by the method. The present invention further provides methods of using the cells.

Abstract: Methods and compositions are provided for detecting molecular translocations, particularly protein translocations within and between subcellular copartments, using at least two components that exhibit a localization-dependent difference in complementation activity. In particular, alpha-complementing ?-galactosidase fragments are provided. These ?-galactosidase reporter fragments display significantly enhanced enzymatic activity when one fragment is localized in a membrane. Methods for carrying out no-wash ELISA assays based on the reporter component system are also provided.

Abstract: The invention provides a hexon Tat-PTD modified adenovirus, a gene delivery vector based on the modified adenovirus that enhances gene delivery efficiency, and an oncolytic agent based on the modified adenovirus that enhances tumor cell killing efficiency and improves therapeutic outcome.

Abstract: The present disclosure relates to recombinant adeno-associated virus (AAV) vector serotype, wherein the capsid protein of AAV serotypes is mutated at single or multiple sites. The disclosure further relates to an improved transduction efficiency of these mutant AAV serotypes. The AAV serotypes disclosed are AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10. The instant disclosure relates to nucleotide sequences, recombinant vector, methods and kit thereof.

Abstract: The present disclosure describes methods of maintaining the phenotype of differentiated cells. Generally, the natural environment of the body is replicated for the differentiated cell. The differentiated cell is plated on a cell culture substrate comprising a laminin, such as laminin-521 or laminin-511. The substrate may also contain a cadherin. This maintains the phenotype of the differentiated cell.

Abstract: The present invention relates to a nucleic acid encoding a polypeptide and the use of the nucleic acid or polypeptide in preventing and/or treating cancer. In particular, the invention relates to improved vectors for the insertion and expression of foreign genes encoding tumor antigens for use in immunotherapeutic treatment of cancer.

Abstract: This invention provides methods and compositions for increasing the efficiency of obtaining pluripotent stem cells, the method comprising expressing a 133p53 in cells that are being re-programmed to obtain pluripotent cells. The invention also provides method of inhibiting the proliferation of cancer stem cells, the method comprising suppressing expression of 133p53 in the cells.