Abstract: The present disclosure provides codon optimized RPGRorf15 sequences, vectors, and host cells comprising codon optimized RPGRorf15 sequences, and methods of treating retinal disorders such as XLRP comprising administering to the subject a codon optimized RPGRorf15 sequence.

Abstract: It is to provide an immunocompetent cell that expresses regulatory factors of immunocompetent cell immune function and possesses all of proliferative potential, viability, and the ability to accumulate a T cell, and an expression vector of regulatory factors of immune function for generating the immunocompetent cell. An immunocompetent cell expressing a cell surface molecule specifically recognizing a cancer antigen, interleukin 7 (IL-7), and CCL19 is generated. Preferably, the cell surface molecule specifically recognizing a cancer antigen is T cell receptor specifically recognizing the cancer antigen, and the immunocompetent cell is a T cell.

Abstract: The present invention relates to the discovery that the expression levels of some RNA molecules, comprising messenger RNA (mRNA), non-coding RNA (ncRNA) and/or microRNA (miRNA), and protein can be used as a diagnostic signature to predict or monitor the bone healing ability in an acutely injured subject or in a chronic nonunion subject. In certain embodiments, the invention relates to methods and compositions useful for differentiating between a nonunion, slow healing, and/or normal healing of a fractured bone and treatment recommendations. The invention further includes a kit comprising biomarker probes for assessing the bone healing ability in an acutely injured subject or in a nonunion subject after receiving therapeutic treatment.

Abstract: The invention provides gene therapy vectors, such as adeno-associated vims (AAV) vectors, expressing a functional fragment of the miniaturized human micro-dystrophin gene and method of using these vectors to express the fragment of micro-dystrophin in skeletal muscles including diaphragm and cardiac muscle and to protect muscle fibers from injury, increase muscle strength and reduce and/or prevent fibrosis in subjects suffering from muscular dystrophy.

Abstract: The present invention relates to a nucleotide-modified messenger RNA for the permanent correction of a genetic alteration on a DNA. The invention further relates to a nucleotide-modified messenger RNA in combination with a repair template. It also relates to a pharmaceutical composition. It finally relates to methods for the correction of a genetic alteration on a DNA.

Abstract: Provided herein are safe harbor loci and methods for identifying and using safe harbor loci to engineer cells to express transgenes. The safe harbor loci exhibit increased transgene knock-in efficiency and allow for increased, stable expression of transgenes in engineered cells. Guide ribonucleic acids (gRNAs) may be used for insertion of transgenes in the safe harbor loci.

Abstract: The present disclosure provides new RNA-guided nucleases for making rational, direct edits to nucleic acids in live cells; specifically, the present disclosure provides Type V MAD nucleases (e.g., RNA-guided nucleases or RGNs) with altered PAM preferences and/or altered activity at different temperatures or fidelity, and/or varied nuclease activities; all changes that may increase the versatility of a nucleic acid-guided nuclease for certain editing tasks.

Abstract: The present disclosure provides donor polynucleotides, genome editing systems, methods, pharmaceutical compositions, and kits which correct or induce a mutation that causes Glycogen Storage Disease 1a in a genomic DNA (gDNA) molecule in a cell. In some embodiments the present disclosure provides donor polynucleotides comprising two strands capable of correcting a mutation that causes Glycogen Storage Disease 1a.

Abstract: Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide; and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence.

Abstract: Provided herein are adeno-associated virus (AAV) compositions that can restore F8 gene function in a cell without co-transducing or co-administering an exogenous nuclease or a nucleotide sequence that encodes an exogenous nuclease. Also provided are methods of using the AAV compositions to correct an F8 gene mutation and/or treat a disease or disorder associated with an F8 gene mutation. Packaging systems for making the adeno-associated virus compositions are also provided.

Abstract: Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Abstract: The present disclosure is directed to methods of scarless genomic engineering in microorganisms, such as Bacillus, and provides for new molecular tools and methods which enable scarless genetic editing using at least one counterselectable marker that has been codon optimized for the microorganism. The disclosure allows for the high-throughput introduction of stable genetic edits to a genome using either plasmid or linear DNA constructs for genetic engineering.

Abstract: Disclosed herein are method of producing NK cells that include one or more heterologous nucleic acids. The methods include culturing a population of isolated NK cells in the presence of one or more cytokines to produce a population of activated NK cells. The population of activated NK cells are transduced with a viral vector comprising the one or more heterologous nucleic acids, for example by contacting the activated NK cells with viral particles including the viral vector. The resulting transduced NK cells are then cultured in the presence of one or more cytokines, and optionally in the presence of irradiated feeder cells, to produce a population of expanded transduced NK cells. Also disclosed are methods of treating a subject with a disorder (such as a tumor or hyperproliferative disorder) by administering to the subject NK cells produced by the methods described herein.

Abstract: A nucleic acid molecule can code for an Orf virus vector promoter. A recombinant Orf virus vector can be included in a cell. The nucleic acid molecule, the vector and/or the cell can be included in a composition. The recombinant Orf virus vector can be used for the production of a foreign gene.

Abstract: A method to produce protein in Aspergillus niger's sleeping spores using single-stranded RNA is provided. The method includes three steps: culture of Aspergillus niger and collection of spores, pretreatment of Aspergillus niger spores, and electroporation of Aspergillus niger spores using HDEN method. Non-germinated spores are used as a starting material for introduction of exogenous molecules. The exogenous protein coding single-stranded RNA is introduced into the resting spores of Aspergillus niger by employing the HDEN electrotransformation technique to express protein. This method is simple and fast, the effect is excellent, and the transformation rate reaches more than 90%.

Abstract: Compositions and methods for AAV mediated gene therapy are disclosed. AAV vectors comprise protein capsid variants comprising therapeutically beneficial transgenes. AAV variants are provided which exhibit increased transduction efficiency when compared to AAV serotypes (e.g., AAV1, AAV2, AAV8, AAV-rh74), which lack the modifications disclosed herein. Such improved vectors are useful for transduction of a variety of tissues.

Abstract: The disclosure relates to compositions comprising and methods for chemical modification of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components. Compositions comprising modified ribonucleic acids have been designed with chemical modification for even higher efficiency as unmodified native strand of sgRNA. Administration of modified ribonucleic acids will allow decreased immune response when administered to a subject, increased stability, increased editing efficiency and facilitated in vivo delivery of sgRNA via various delivery platforms. The disclosure also relates to methods of decreasing off-target effect of CRISPR and a CRISPR complex.

Abstract: This invention relates to the treatment of age-related disorders with a combination of the hTERT gene and the Follistatin gene in a delivery system such as in an adeno-associated viral vector. The Follistatin gene is expected to promote the division of stem cells that will regenerate the organism and the hTERT will prevent their depletion.

Abstract: Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE-induced toxicity.

Abstract: The present invention relates to the field of (vector) vaccines, and especially to novel promoter sequences, expression cassettes and vectors, which are suitable to express genes of interest, especially antigen encoding sequences. The viral vectors of the present invention are useful for producing an immunogenic composition or vaccine.