Abstract: The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAAV9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: There is described a chimeric antigen receptor (CAR) which comprises an antigen binding domain which selectively binds to Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1), and its use. Also described is a T cell comprising the CAR and its use in the treatment of cancer.

Abstract: Provided are plasmid vector constructs encoding multiple immunomodulatory proteins where each protein or component thereof can be expressed utilizing appropriate promotors and/or translation modifiers. Additional immunomodulatory proteins and genetic adjuvants containing shared tumor antigens can be added to further therapeutic potential as well as allow tracking of therapeutic treatment. Also provides are methods of expressing the plasmid constructs.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Abstract: The present invention relates to a cell line, use of the cell line and a method for producing infectious viral particles using said cell line.

Abstract: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Abstract: Provided are vaccines for eliciting an immune response. The vaccines for eliciting an immune response comprise RNA encoding an immunogen, which is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: Provided are vaccines for eliciting an immune response. The vaccines for eliciting an immune response comprise RNA encoding an immunogen, which is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: The invention concerns a multicistronic nucleic acid, in particular an isolated multicistronic nucleic acid, comprising: A) a sequence comprising successively: A1) a sequence encoding the light chain variable domain of an antibody of interest, fused in the frame with A2) a sequence encoding the constant region of the light chain of an immunoglobulin Ig; and B) a sequence comprising successively: B1) a sequence encoding the heavy chain variable domain of said antibody of interest, fused in the frame with B2) a sequence encoding the constant regions of the heavy chain of an immunoglobulin Ig? in secretory form; B3) an intronic sequence of the gene of the heavy chain of said immunoglobulin Ig?, said intronic sequence comprising an internal 5? splice site enabling the splicing of said intronic sequence B3) and a secretory-specific poly(A) (p AS) signal from the 3? terminal exon of said gene; B4) a sequence, in frame with sequence B1), encoding the transmembrane and cytoplasmic domains M1 and M2 of the immunoglobu

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Abstract: Methods of designing a polynucleotide sequence for expressing a polypeptide-of-interest in a cell are provided. Also provided are artificial transcript sequences generated according to the present teachings. Further provided are methods of estimating the adaptiveness of a transcript sequence encoding a polypeptide-of-interest to a gene expression machinery in a cell.

Abstract: The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

Abstract: The present invention relates to a nucleic acid coding for a human DGKk protein lacking a functional Proline Rich Region and/or a functional EPAPE repeated Region, and to its use in the treatment of fragile X syndrome in a patient in need thereof.

Abstract: Disclosed herein are immunogenic compositions for producing immediate and sustained immunity to infectious viral and bacteriological pathogens. A univalent immunogenic composition is disclosed comprising an isolated antigen and a polynucleotide formulated into a nanoparticle or liposome. Furthermore, multivalent immunogenic compositions are disclosed comprising multiple univalent immunogenic compositions. Also disclosed, are methods of inducing protective or therapeutic immune responses in individuals comprising administering one or more univalent immunogenic compositions.

Abstract: Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Abstract: The present application provides materials and methods for treating a patient with one or more condition associated with FXN whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of FXN gene in a cell by genome editing.

Abstract: This invention provides WT1 peptides and methods of treating, reducing the incidence of, and inducing immune responses against a WT1-expressing cancer, comprising same.

Abstract: The present invention relates to an RNA encoding a therapeutic protein, in particular a collagenase, growth factor, cytokine, receptor, chaperone or signal transduction inhibitor. In particular, the present invention relates to RNA suitable for treatment of wounds, specifically for promoting wound healing. The present invention concerns such RNA as well as pharmaceutical compositions and kits and combinations comprising the RNA. Furthermore, the present invention relates to the RNA, pharmaceutical compositions, kits as disclosed herein for use in the treatment of wounds, specifically for promoting wound healing.