Abstract: The invention in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the invention relates to gene transfer methods using the recombinant adeno-associate viruses. In some aspects, the invention relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Abstract: Methods for the rapid amplification of extremely low quantity nucleic acids in a sample are provided. The disclosed methods are capable of amplifying less than 1 pg of DNA and/or RNA from a biological sample using a single tube and one-step or two-step preparation.

Abstract: A CRISPR/Cas system and method for editing or regulating transcription of a genome of a cell are provided, wherein the system includes a Cas endonuclease fused with one or more degron sequences and at least one activatable cognate single guide RNA harboring an inactivation sequence in a non-essential region of the cognate sgRNA, wherein said inactivation sequence comprises one or more endonuclease recognition sites of, e.g., a ribozyme.

Abstract: Provided herein is a previously unannotated lncRNA lying within exon six and 3?UTR of the LCK gene, labeled “HULLK” for Hormone-Upregulated lncRNA within LCK. HULLK is a novel lncRNA situated within the LCK gene that can serve as an oncogene in PCa. Accordingly, provided are methods and compositions for diagnosing and treating prostate cancer based on HULLK that regulates prostate cancer cell growth.

Abstract: The present disclosure generally relates to polynucleotides and AAV vectors that provide for the expression of ALD protein in target (e.g., neurons or glial) cells when administered to subjects in need thereof. The present disclosure further relates to compositions comprising such a polynucleotide or vector. These polynucleotides, vectors, and compositions may be used for the treatment and prevention of ALD or AMN in subjects in need thereof.

Abstract: Compositions and regimens useful in treating hemophilia A are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Factor VIII.

Abstract: In a first aspect, the present invention relates to a mutated adeno-associated virus (AAV) capsid protein or fragment thereof wherein a substitution of a wild type non-cysteine amino acid into a cysteine is present whereby the wild type non-cysteine amino acid is exposed on the outer surface of the capsid of an AAV particle. In a further aspect, a mutated AAV particle comprising the AAV capsid protein or fragment thereof according to the present invention is provided. In addition, a nucleic acid encoding the AAV capsid protein according to the present invention is identified together with a corresponding nucleic acid vector, in particular, a plasmid or a gene string. In addition, a host cell containing the nucleic acid vector or the nucleic acid according to the present invention as well as a composition comprising at least an infectious (transducing) AAV particle containing a mutated AAV capsid protein as defined herein together with a non-infectious AAV particle containing a mutated AAV capsid protein as e.

Abstract: Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (for example, variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.

Abstract: The present invention relates to isolated polynucleotide and polypeptide sequences derived from novel chimpanzee adenovirus ChAd157, as well as to recombinant polynucleotides, vectors, adenoviruses, cells and compositions comprising said polynucleotide and polypeptide sequences.

Abstract: The present invention provides a method for preparing a coronavirus-targeting universal DC cell vaccine, and belongs to the technical field of virus vaccine preparation. The preparation method includes the following steps: ligating a fusion gene including a HLA gene and a coronavirus antigen gene onto an expression vector to obtain a recombinant vector; then transferring the recombinant vector into antigen-presenting cells to be transfected to obtain the coronavirus-targeting universal DC cell vaccine. The universal DC cell vaccine of the present invention has a targeting property against a coronavirus, can effectively stimulate a CTL, and has a killing effect on a target cell.

Abstract: The present disclosure provides recombinant adeno-associated virus virions with variant capsid protein, where the recombinant AAV (rAAV) virions exhibit one or more of increased ability to cross neuronal cell barriers, increased infectivity of a neural stem cell, increased infectivity of a neuronal cell, and reduced susceptibility to antibody neutralization, compared to a control AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a neural stem cell or a neuronal cell in an individual. The present disclosure also provides methods of modifying a target nucleic acid present in a neural stem cell or neuronal cell.

Abstract: The present invention relates to a Pde6b-deficient animal model of retinal degeneration produced by engineered endonucleases, and a method for producing the same. In the animal model of retinal degeneration according to the present invention, only a specific target gene can be removed using engineered endonucleases, so that mutagenesis can be stably achieved. In addition, it is possible to produce a congenital animal model through genetic manipulation at the embryonic stage rather than through acquired factors, which allows for production of an animal model that uniformly exhibits symptoms of the disease in question without being influenced by other factors.

Abstract: The invention provides adenoviral vectors comprising transgenes encoding Chikungunya virus antigens. The vectors can be used to produce vaccines for the prophylaxis, amelioration and treatment of diseases caused by Chikungunya virus infections.

Abstract: The present disclosure provides methods and compositions of modulating expression of a target nucleic acid in a eukaryotic cell. The methods include providing to the cell a guide RNA complementary to the target nucleic acid sequence, providing to the cell a fusion protein, wherein the fusion protein comprises a nuclease null Cas9 protein and a transcriptional effector domain, wherein the nuclease null Cas9 protein interacts with the guide RNA and binds to the target nucleic acid sequence in a site specific manner and wherein the transcriptional effector domain modulates expression of the target nucleic acid.

Abstract: Disclosed herein are compositions related to conjugated polypeptides with MTA/ADO-degrading enzyme activity. The conjugated polypeptides are engineered to allow for maximal conjugation while maintaining catalytic activities. Also disclosed are nucleic acids, expression vectors, and host cells related to the conjugated polypeptides. Further disclosed are methods of using the pharmaceutical formulations comprising above to treat cancer.

Abstract: A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.

Abstract: Disclosed herein are methods of producing chimeric antigen receptor (CAR) T cells using substrates, such as artificial antigen presenting cells, containing on a surface a a heparin binding domain (HBD), anti-CD3 single chain antibodies, anti-CD28 single chain antibodies (scFv), and optionally anti-41BBL antibodies. Anti-CD3 and Anti-CD28 scFvs bind and activate expanding T cells ex vivo, while the Heparin Binding Domain binds the viral vector, thereby bringing the T cells into close proximity with virus for effective gene transfer. This is a less costly, renewable, modifiable, and efficacious alternative to coated beads and RetroNectin® for gene transfer.

Abstract: Described herein are methods and related compositions for inducing differentiation of human pluripotent stem cells (hPSCs) into hemogenic endothelium with pan-myeloid potential or restricted potential, by forced expression in the hPSCs of a combination of transcription factors as described herein.

Abstract: The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.

Abstract: The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.

Abstract: Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.

Abstract: The present invention relates to a pharmaceutical composition for preventing or treating cancer comprising cancer antigen-specific cytotoxic T cells; the pharmaceutical composition comprises about 7×106 cells/mL or more, and of the about 7×106 cells/mL, about 90% or more are CD8+ T cells.

Abstract: Provided are methods and compositions for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites. Also provided are cell populations or clonal cell lines derived from genome-engineered iPSCs, which comprise targeted integration of one or more exogenous polynucleotides, and/or in/dels in one or more selected endogenous genes.

Abstract: The invention provides methods for treating neurological disorders, which involve administering therapeutic agents to the thalamus by convection enhanced delivery.

Abstract: A gRNA molecule includes a first domain complementary to at least a portion of TCOF1 gene, and a second domain for binding with Cas9 protein, and a kit includes the gRNA molecule. A method of treating a subject suffering from a cancer associated with an elevated expression of TCOF1 gene includes the step of administering an effective amount of a first recombinant vector comprising the gRNA molecule of the invention to the subject. A method of inhibiting the expression of TCOF1 gene in cancer cells associated with an elevated expression of TCOF1 gene includes contacting the cancer cells with a first recombinant vector, wherein the first recombinant vector comprises a gRNA molecule comprising a first domain complementary to at least a portion of TCOF1 gene and a second domain binding with Cas9 protein.

Abstract: Provided herein are methods for generating reversion free attenuated and/or replication incompetent vaccine vectors and their use in vaccine compositions and vaccination. In particular, the use of a codon shuffled helper gene is used to produce compositions comprising replication incompetent virus.

Abstract: The present invention provides methods of reprogramming cells, for example, directly reprogramming a somatic cell of a first cell type into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for reprogramming a cell of an endoderm origin to a cell having pancreatic ?-cell characteristics. The present invention also relates to an isolated population comprising reprogrammed cells, compositions and their use in the treatment of diabetes mellitus. In particular, the present invention relates to reprogramming a cell of an endoderm origin to a cell having pancreatic ?-cell characteristics by increasing the protein expression of at least one transcription factor selected from Pdx1, Ngn3 or MafA in the cell of endoderm origin to reprogram the cell of an endoderm cell to a cell which exhibits at least one or at least two characteristics of an endogenous pancreatic ?-cell.

Abstract: Genetically modified compositions, such as adeno-associated viral vectors and primary cells, for treating various conditions and diseases. Disclosed are also modified adeno-associated viruses for the treatment of cancer. Also disclosed are the methods of making and using the genetically modified compositions in treating various diseases, conditions, and cancer.

Abstract: The present invention relates generally to a fusion protein that when displayed on a cell can convert a negative signal into a positive signal in the cell. The fusion protein is a chimeric protein in that the protein comprises at least two domains, wherein the first domain is a polypeptide that is associated with a negative signal and the second domain is a polypeptide that is associated with a positive signal. Thus, the invention encompasses switch receptors that are able to switch negative signals to positive signals for enhancement of an immune response.

Abstract: The present invention relates generally to immunotherapy for preventing HIV infection in HIV-negative individuals. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Abstract: The present invention relates generally to a gene expression system utilizing an alphavirus replicon and T7 promoter. The system is capable of expressing proteins in the cell cytoplasm without integrating the gene of interest into the genome of a host cell. The invention has a wide range of applications such as producing induced pluripotent cells and vaccines against pathogens and cancers.

Abstract: Described herein are reprogramming techniques allowing for production of mammary-derived iPSCs (“m-iPSCs”). The m-iPSCs described herein exhibit all the hallmarks of stem cell identity including round cluster, bright colony morphology, clonal expansion, and pluripotent marker expression (alkaline phosphatase expression, Oct-4, nanog, etc.) Further refined techniques allow for generation of m-iPSCs under essentially defined conditions.

Abstract: The present invention relates to particles comprising protamine, RNA and at least one endosome destabilizing agent, to methods of their production and to pharmaceutical compositions or kits containing the particles. It further relates to particles comprising protamine and RNA for use in methods of treatment or prevention of diseases and to kits comprising such particles together with at least one endosome destabilizing agent.

Abstract: The disclosure provides novel large serine recombinases and their respective recognition sites, as well as libraries of orthogonal recombinase recognition sites. Uses of the large serine recombinases, recognition sites, and libraries of orthogonal recombinase recognition sites also are provided.

Abstract: Provided herein is a nucleic acid comprising consensus amino acid sequence of foot-and-mouth disease FMDV VP1-4 coat proteins of FMDV subtypes A, Asia 1, C, O, SAT1, SAT2, and SAT3 as well as plasmids and vaccines expressing the sequences. Also provided herein is methods for generating an immune response against one or more FMDV subtypes using the vaccine as described above as well as methods for deciphering between vaccinated mammals with the vaccine and those that are infected with FMDV.

Abstract: Sequences of novel adeno-associated virus capsids 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. AAV-mediated delivery of therapeutic and immunogenic genes using the vectors of the invention is also provided.

Abstract: The present invention relates to a method for preparing induced dopaminergic neuronal progenitors (iDPs) comprising inducing an expression of Oct4, Sox2, Klf4, and c-Myc genes in adult cells and direct reprogramming of the adult cells to the iDPs by treating the cells with sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF8); and a cell therapy product and a composition for treating or preventing Parkinson's Disease (PD) which comprises the iDPs as active ingredients. In addition to this, the present invention relates to a method for preparing midbrain dopaminergic neurons comprising isolating NSC-like colony by culturing the iDPs, dissociating the isolated NSC-like colony, and culturing the cells on the neural cell differentiation medium. Further, the present invention relates to a method for treating PD or a method for screening medicine for preventing or treating PD using the cells of the present invention.

Abstract: The present invention provides mutant adeno-associated virus (AAV) that exhibit altered capsid properties, e.g., reduced binding to neutralizing antibodies in serum and/or altered heparin binding and/or altered infectivity of particular cell types. The present invention further provides libraries of mutant AAV comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV and mutant AAV libraries, and compositions comprising the mutant AAV. The present invention further provides recombinant AAV (rAAV) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins, and host cells comprising the nucleic acids. The present invention further provide methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

Abstract: The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.

Abstract: The present invention provides a method for generation of a cell composition of mesencephalic dopaminergic progenitor cells from a starting cell composition comprising pluripotent and/or multipotent stem cells, the method comprising the steps of a) differentiating said pluripotent and/or multipotent stem cells into mesencephalic dopaminergic progenitor cells, thereby generating a cell population comprising mesencephalic dopaminergic progenitor cells and other cells, b) dissociating the differentiated cells of step a) into a single cell suspension, and c) enriching said mesencephalic dopaminergic progenitor cells by using an antigen binding molecule specific for the CD47 antigen for positive selection of said mesencephalic dopaminergic progenitor cells in said single cell suspension. Said method may be performed in a closed cell sample processing system and may be performed in an automated manner.

Abstract: The invention relates to methods for isolating traffic-enhancing mutants of drug delivery proteins. In one embodiment, the invention provides a carrier for delivering a therapeutic agent to an organelle, comprising a polypeptide encoded by a mutant penton base gene. In another embodiment, the invention provides a method of enhancing trafficking to a cell by administering a composition comprising a penton base (PB) protein with one or more mutations that enhance cellular entry.

Abstract: The present invention provides vectors that contain and express in vivo or in vitro FeLV antigens that elicit an immune response in animal or human against FeLV, compositions comprising said vectors and/or FeLV polypeptides, methods of vaccination against FeLV, and kits for use with such methods and compositions.

Abstract: The invention features nucleic acid constructs encoding chimeric immune T-cell receptors (CIRs) that are useful for treating HIV in patients. In general, the CIRs contain an extracellular domain which targets HIV or HIV infected cells (e.g., the extracellular domain of CD4), a transmembrane domain, and a cytoplasmic domain for mediating T-cell activation (e.g., CD3 zeta and/or the partial extracellular domain of CD28). The invention also features the use of host cells expressing CIRs in the treatment of HIV.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Disclosed are viral vector compositions comprising polynucleotide sequences that express one or more biologically-active mammalian guanylate cyclase proteins. Also disclosed are methods for their use in preventing, treating, and/or ameliorating at least one or more symptoms of a disease, disorder, abnormal condition, or dysfunction resulting at least in part from a guanylate cyclase deficiency in vivo. In particular embodiments, the use of recombinant adeno-associated viral (rAAV) vectors to treat or ameliorate symptoms of Leber's congenital amaurosis, as well as other conditions caused by an absence or reduction in the expression of a functional retinal-specific guanylate cyclase 1 (retGC1).

Abstract: The teachings herein are generally directed to a method of enhancing the genetic stability of parvovirus vectors. The stability of conventional ss or dsAAV vector constructs can be enhanced, for example, to obtain a concurrent increase in vector titer and purity, as well as an improvement in vector safety, due at least in part to the elimination of stuffer DNA from the AAV vector. The method is broadly applicable to all gene transfer/therapy applications, such as those requiring delivery of foreign DNA containing recombinant gene expression cassettes. Such foreign DNA can range, for example, from about 0.2 up to about 5.2 kb in length. The enhanced vector constructs are highly flexible, user-friendly, and can be easily modified (via routine DNA cloning) and utilized (via standard AAV vector technology) by anyone skilled in the art.

Abstract: Vaccine compositions for use in inducing enhanced antigen-specific T cell-mediated immune responses in a subject in need thereof are disclosed. The composition comprises (a) a therapeutically effective amount of an immunogenic protein comprising at least an antigen of a pathogen; (b) a saponin-base adjuvant selected from the group consisting of GPI-0100, Quil A, QS-21; and (c) a Toll-like receptor (TLR) agonist adjuvant selected from the group consisting of monophosphoryl lipid A (MPL), and CpG1826.

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: 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.