The disclosure is directed to an expression vector or a combination of at least two expression vectors for producing a polypeptide of interest, the vector or vectors comprising a polynucleotide encoding a mutated folate receptor as a selectable marker. The disclosure also relates to host cells, selection methods and methods for producing polypeptides with high yield.

Provided herein are methods and compositions for treating an eye disorder, for example cone-rod dystrophy type 6 (CORD6). In certain aspects, a therapeutically effective amount of a composition comprising nucleic acids is administered to a subject to treat an autosomal dominant disorder or condition, such as a condition associated with a dominant mutation in a guanylate cyclase 2D (GUCY2D) gene, such as knocking out a dominant mutant form of the gene in the subject. Further provided herein are recombinant AAV particles that comprise one or more recombinant AAV genomes comprising nucleic acids that encode a guide RNA that targets a GUCY2D gene and/or an RNA-guided endonuclease.

Disclosed herein are products, methods, and uses for a new gene therapy for treating, ameliorating, delaying the progression of, and/or preventing a muscular dystrophy involving a mutation amenable to DNA repair including, but not limited to, any mutation involving, surrounding, or affecting various regions of the DMD gene. Specifically, the disclosure provides products and methods for fixing diverse DMD mutations by replacement of large segments of the DMD gene comprising multiple exons, using CRISPR/Cas9 and Homology-Independent Targeted-Integration (HITI) to accomplish high efficiency knock-in or make large replacements using the non-homologous end-joining (NHEJ) DNA repair pathway, previously not achievable. In particular, the disclosure provides products, methods and uses for the replacement of DMD exons 1-19, 2-19, or 41-55.

An anterograde monosynaptic transneuronal viral tracer system for mapping the direct postsynaptic targets of neurons in a given brain nucleus comprises a tracer H129-derived recombinant HSV-1 virion; and a helper AAV2/9-derived recombinant AAV2/9 virion; wherein the tracer H129-derived recombinant HSV-1 virion comprises a recombinant HSV-1-H129 viral genome with an impaired gK gene, and a mutant gK protein that pseudotypes the tracer H129-derived recombinant HSV-1 virion; and wherein the helper AAV2/9-derived recombinant AAV2/9 virion comprises a recombinant AAV2/9 viral genome that contains an HSV-1 H129 wild-type gK encoding sequence.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

The present invention concerns a production bacterial cell for producing phage particles or phage-derived delivery vehicles, said production bacterial cell stably comprising at least one phage structural gene(s) and at least one phage DNA packaging gene(s), said phage structural gene(s) and phage DNA packaging gene(s) being derived from a first type of bacteriophage, wherein the expression of at least one of said phage structural gene(s) and/or at least one of said phage DNA packaging gene(s) in said production bacterial cell is controlled by at least one induction mechanism, and wherein said production bacterial cell is from a bacterial species or strain different from the bacterial species or strain from which said first type of bacteriophage comes and/or that said first type of bacteriophage targets.

The invention provides a method for determining whether a human immunodeficiency virus is resistant to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.