Abstract: Aspects of the invention described herein include methods of treating, inhibiting, ameliorating and/or eliminating a virus or cancer cells in a subject utilizing genetically engineered human T-cells having receptors for a molecule presented by the virus or the cancer cells, wherein the genetically engineered T cells are isolated utilizing a two-stage MTX selection that employs increasing concentrations of MTX.

Abstract: The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.

Abstract: A recombinant oncolytic virus with improved safety and anticancer effect and a use thereof are disclosed. The recombinant oncolytic virus is obtained by inserting an HSV-TK fragment-encoding gene into a TK gene region to delete TK of Vaccinia virus. The oncolytic virus expresses an HSV-TK fragment to phosphorylate GCV so that cancer cells infected with the oncolytic virus and their neighboring cancer cells can be killed. GCV is also involved in the suppression of viral proliferation and thus can control side effects caused by a virus even upon the administration of a high dose of the virus.

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: Described herein are compositions comprising subsets of monocyte having distinct functional properties and methods for using the same to treat infectious disease.

Abstract: The invention provides methods of treating metastatic or unresectable pancreatic cancer through the administration of a combination of an immune modulator and radiation therapy.

Abstract: The present invention relates to a composition for gene transfer comprising a recombinant virus vector and provides a composition for gene transfer which improves the efficiency of gene transfer using a virus vector. Specifically, the present invention provides a composition for gene transfer, which comprises a recombinant virus vector comprising a gene of interest for expression and a sugar at a concentration of at least 40 mM. The virus vector is preferably an adeno-associated virus vector. By using the composition of the present invention, the efficiency of gene transfer using a virus vector can be improved by about 50 times or more.

Abstract: The present invention relates to a biologic that inhibits angiogenesis. In particular, the present invention relates to fusion proteins that inhibit the integrin activated pathway and one other angiogenic factor-activated pathway, the compositions of these fusion proteins, as well as methods for producing and using the same.

Abstract: The present disclosure provides adeno-associated virus (AAV) vectors, comprising coevolved capsid variant proteins, pharmaceutical compositions, methods of making, and methods for delivering such to a subject.

Abstract: The disclosure is directed in part to variant capsid polypeptides that can be used to deliver payloads.

Abstract: A method for assisting in cell isolation from a biological tissue section includes: obtaining cell images that are each an image of cells isolated from the biological tissue section, the biological tissue section being soaked in a solution containing an enzyme; calculating, from the cell images, a number of the cells isolated from the biological tissue section as an indicator of the cell isolation from the biological tissue section; and visualizing a temporal change in the indicator on the basis of a history of the indicator.

Abstract: The present invention relates to a novel adenoviral vector not including a replication competent adenovirus. A recombinant E1/E3/E4-deleted adenoviral vector, of the present invention, in which an antigenic protein and an E4orf6 gene are inserted in an E1 gene-deleted region, has adenovirus productivity, degree of antigen expression, neutralizing antibody production amount, and T cell induction ability that are similar to those of a control group, and thus can be effectively used as a carrier for various vaccines for diseases or anti-cancer vaccines.

Abstract: Disclosed are systems and methods that include or utilize composable mammalian elements of transcription (COMET) including engineered recombinant proteins that regulate transcription and engineered DNA promoter sequences that are regulated by the engineered recombinant proteins. The elements may be composed to form logic gates, gene expression cascades and programs, and cell-based biosensors.

Abstract: Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Abstract: The present invention relates to methods of rescue and/or propagation of paramyxovirus species, particularly wherein both rescue and propagation are carried out in the same cell type; i.e., without the use of helper cells for viral rescue. The paramyxoviruses produced by the disclosed methods may encompass wild-type viruses, chimeric viruses, recombinant viruses or engineered viral products such as virus like particles (VLP). Viruses and/or viral products produced in the method according to the current invention are suitable for medical or veterinary use in such applications as treating or preventing infectious diseases, particularly avian paramyxovirus and human respiratory virus infections, and cancer treatment.

Abstract: Implementations are described that relate to methods and systems for growing cells in a hollow fiber bioreactor. In implementations, the cells may be exposed to a number of growth factors including a combination of recombinant growth factors. In other implementations, the cells may be grown in co-culture with other cells, e.g., hMSC's. In implementations, the cells may include CD34+ cells. A coated membrane includes a membrane having a first coating configured to promote cellular adhesion to the membrane and a second coating that includes a soluble protein moiety.

Abstract: The present invention relates to the prevention and/or treatment of retinal dystrophy in a patient, including Leber congenital amaurosis (LCA).

Abstract: Disclosed herein, are recombinant polypeptides comprising one or more homologous amino acid repeats; and, non-immunogenic bioconjugates comprising recombinant polypeptides comprising one or more homologous amino acid repeats and one or more therapeutic agents. Also, disclosed herein are pharmaceutical compositions including the recombinant polypeptides; and methods of administering the recombinant polypeptides to patients for the treatment of cancer or infections.

Abstract: The present invention discloses an in-vitro method for transferring biological material into activated NK cells with a pseudotyped retroviral vector particle or a virus-like particle thereof, comprising the steps a) activation of NK cells, and b) addition of said pseudotyped retroviral vector particle or virus-like particle thereof to said activated NK cells, wherein said pseudotyped retroviral vector particle or virus-like particle thereof comprises a modified baboon endogenous retrovirus (BaEV) envelope glycoprotein that is able of binding to and fusing with a hematopoietic cell membrane, thereby transferring biological material into said activated NK cells. Preferentially, the activating of NK cells is performed by the addition of a IL-1 family cytokine to the NK cells.

Abstract: Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.

Abstract: Provided herein are compositions, methods, kits, and viral particles for treating a disease or disorder associated with a deep intronic mutation using an engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) (CRISPR-Cas) system. In some aspects, provided herein is a self-limiting CRISPER-Cas system.

Abstract: The disclosure, in some aspects, relates to methods and compositions for recombinant adeno-associated virus (rAAV)-mediated delivery of genome editing molecules to a pre-implantation embryo.

Abstract: An adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein each transgene encodes an RSV antigenic protein or a fragment thereof.

Abstract: Compositions providing, and methods for providing and using, targeted rAAV are disclosed.

Abstract: The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, e.g., which include an annexin core domain to mediate efficient antigen delivery and antigen presentation in order to induce an antigen-specific immune response and/or to treat or prevent infectious diseases and/or cancer.

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: 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: 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: 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: 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: 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: 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: 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.