Abstract: Provided herein are recombinant constructs, vectors and expression cassettes including a first promoter which is suitably a tRNA promoter operably connected to a first polynucleotide encoding a first single guide RNA and a second promoter operably connected to a second polynucleotide encoding a Cas9 polypeptide. The first single guide RNA includes a first portion complementary to a strand of a target sequence of a DNA virus and a second portion capable of interacting with the Cas9 polypeptide. Also provided are codon optimized Staphylococcus aureus derived Cas9 polynucleotides and polypeptides with nuclear localization signals and optionally an epitope tag. Also provided are constructs for production of sgRNAs including a tRNA. Methods of inhibiting viral replication, inhibiting expression of a target sequence from a virus or treating a viral infection or viral induced cancer using the compositions are also provided.

Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: This disclosure describes a composition and method of magnetic nanoparticles (MNP) that are bound to a baculovirus (BV). The MNP-BV can be systemically administered to a patient, and a strong magnetic field applied to the target tissue, thus allowing uptake and expression only in the target tissue. Off-target effects are not seen because the MNP-BC is inactivated by the complement system outside of the magnetic field.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: The present invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain specific for SSEA4, a population of engineered cells expressing said CARs, and a pharmaceutical composition comprising said genetically modified cells expressing said CARs. The pharmaceutical composition may be for use of the treatment of cancer in a subject suffering from cancer, wherein at least a subpopulation of the cancerous cells of said cancer expresses SSEA4.

Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilisation step wherein the filter-sterilisation step is not the final step in the purification process.

Abstract: Embodiments of the invention concern copolymers and nanoparticles for use as delivery agents for one or more agents for therapy for a medical condition of humans and animals. Some of embodiments of the invention provide new reagents for biomedical research in cell culture, animal models and plants, for example. The copolymers comprise PLGA and PEI and, in some embodiments, also comprise 1-(3-aminopropyl)-4-methylpiperazine (APMP), Fc binding peptide and/or antibody. In certain embodiments, APMP-PLGA-PEI, Fc binding peptide/antibody-PLGA-PEI or Fc binding peptide/antibody-AP-MP-PLGA-PEI nanoparticles comprising one or more therapeutic agents are delivered to an individual in need thereof or used for biomedical research in cell cultures, animal models and plants.

Abstract: Composition containing a microorganism, preferably an Archaea, expressing a TMA methyltransferase and a TMA methyl group acceptor corrinoid protein, capable of metabolizing trimethylamine (TMA) in the presence of hydrogen in a human cavity, such as the intestine or the vagina, for use as a medicament for treating, reducing or eliminating TMA at the level of the human cavity. In addition, a composition containing a TMA methyltransferase and a TMA methyl group acceptor corrinoid protein. These compositions are of use for treating trimethylaminuria, for treating vaginal fluids in the case of bacterial vaginosis and for reducing or eliminating odours due to TMA. These compositions are also of use for reducing the level of plasma TMAO, for preventing the formation of atheroma plaques and/or for preventing cardiovascular diseases.

Abstract: Systems and methods for detecting and/or identifying target cells (e.g., bacteria) using engineered transduction particles are described herein. In some embodiments, a method includes mixing a quantity of transduction particles within a sample. The transduction particles are associated with a target cell. The transduction particles are non-replicative, and are engineered to include a nucleic acid molecule formulated to cause the target cell to produce a series of reporter molecules. The sample and the transduction particles are maintained to express the series of the reporter molecules when target cell is present in the sample. A signal associated with a quantity of the reporter molecules is received. In some embodiments, a magnitude of the signal is independent from a quantity of the transduction particle above a predetermined quantity.

Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.

Abstract: The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.

Abstract: The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

Abstract: CRISPR-Cas genome editing uses a guide RNA, which includes both a complementarity region, which binds the target DNA by base-pairing, and a Cas9-binding region, to direct a Cas9 nuclease to a target DNA. Further disclosed are methods for increasing specificity of RNA-guided genome editing using CRISPR/Cas9 systems by using truncated guide RNAs (tru-gRNAs).

Abstract: The invention relates to an isolated nucleic acid molecule comprising at least one promoter that is active in fungal cells of the trichoderma species, wherein a nucleic acid sequence encoding an N-acetylglucosamine-2-epimerase and/or an N-acetylneuraminic acid synthase is operatively bound to each promoter. The at least one promoter that is active in fungal cells is a constitutive promoter.

Abstract: A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways.

Abstract: The present invention relates generally to systems and methods for preparing, storing, shipping and using skin equivalents made by organotypic culture. In particular, the present invention relates to systems and methods for cryopreserving viable skin substitutes.

Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.

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: The present disclosure provides novel methods for increasing ?-cell viability in islets by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to the islets. The disclosure also provides novel methods for treating a disease or condition in a subject, such as type 1 diabetes mellitus, by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to islets and transplanting the islets into the subject to treat the disease or condition. Kits and compositions including RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, are also provided to increase ?-cell viability.

Abstract: The invention provides, inter alia, methods for treating vascular deficiencies, including those in diabetic subjects, by transplanting endothelial progenitor cells with transiently reduced p53 expression.