Abstract: The present invention relates to methods of suppressing the transcriptional expression of one or more genes by methylating the chromatin histone proteins of the one or more genes. Specifically, a viral SET domain histone lysine mehtyltransferase (vSET or vSET-like protein) methylates lysine 27 of a gene's histone protein 3 (H3-K27) thereby suppressing the transcription of the gene.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles.

Abstract: The present invention provides novel mitochondrial fusion transcripts and the parent mutated mtDNA molecules that are useful for predicting, diagnosing and/or monitoring cancer. Hybridization probes complementary thereto for use in the methods of the invention are also provided.

Abstract: Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Abstract: A translational control method using an RNA-protein interaction motif is provided. The method comprises a step of introducing an mRNA having: a 5?UTR regulation structure comprising: (1) a cap structure at the 5? terminus, (2) a spacer positioned on the 3? side of the cap structure, and (3) one or more RNA motifs positioned on the 3? side of the spacer, which comprises an RNA-protein interaction motif-derived nucleotide sequence or a variant thereof; and a nucleotide sequence encoding a target protein gene on the 3? side of the 5?UTR regulation structure, into a cell in the presence of a protein specifically binding to the RNA motifs, wherein a translational level is decreased as the number of bases of the spacer decreases, and the translational level is decreased as the number of the RNA motifs increases.

Abstract: The present disclosure provides engineered Class 1 Type I CRISPR-Cas (Cascade) systems that comprise multi-protein effector complexes, nucleoprotein complexes comprising Type I CRISPR-Cas subunit proteins and nucleic acid guides, polynucleotides encoding Type I CRISPR-Cas subunit proteins, and guide polynucleotides. Also, disclosed are methods for making and using the engineered Class 1 Type I CRISPR-Cas systems of the present invention.

Abstract: An isolated nucleic acid sequence encoding the yeast NDI1 protein of SEQ ID NO: 542 or a functional variant thereof is described. The nucleic acid sequence comprises at least 50 codons which are codon optimized compared with the sequence of yeast NDI1 gene of SEQ ID NO: 1.

Abstract: The present invention provides mutant adeno-associated virus (AAV) that exhibit altered capsid properties, e.g., reduced binding to neutralizing antibodies in serum and/or altered heparin binding and/or altered infectivity of particular cell types. The present invention further provides libraries of mutant AAV comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV and mutant AAV libraries, and compositions comprising the mutant AAV. The present invention further provides recombinant AAV (rAAV) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins, and host cells comprising the nucleic acids. The present invention further provide methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

Abstract: The present invention provides nucleic acid molecules, DNA constructs, plasmids, and methods for post-transcriptional regulation of gene expression using RNA molecules to both repress and activate translation of an open reading frame. Repression of gene expression is achieved through the presence of a regulatory nucleic acid element (the cis-repressive RNA or crRNA) within the 5? untranslated region (5? UTR) of an mRNA molecule. The nucleic acid element forms a hairpin (stem/loop) structure through complementary base pairing. The hairpin blocks access to the mRNA transcript by the ribosome, thereby preventing translation. In particular, in embodiments of the invention designed to operate in prokaryotic cells, the stem of the hairpin secondary structure sequesters the ribosome binding site (RBS). In embodiments of the invention designed to operate in eukaryotic cells, the stem of the hairpin is positioned upstream of the start codon, anywhere within the 5? UTR of an mRNA.

Abstract: Methods for assessing infertility and related pathologies and informing treatment type and timing thereof are provided. According to certain embodiments, methods of the invention include determining levels of one or more transcripts present in a sample obtained from a subject suspected of having endometriosis, identifying transcript levels that correspond to a regulation pattern specific to a time-point in a uterine cycle, and characterizing endometriosis of the subject based upon the identified transcript levels. The invention includes methods for assessing age-associated increase in aneuploidy rates based on FSH levels and IVF success rates based on obesity in PCOS patients.

Abstract: The invention relates to methods and materials that can be used to product cytotoxic T cells that target cancer cells expressing the cancer-testis antigen NY ESO-1. Illustrative embodiments of the invention include peripheral blood stem cells transduced with a lentiviral vector that comprises a codon optimized TCR alpha and beta chain polypeptides specific for NY ESO-1. These gene-modified cells are useful, for example, in a hematopoietic stem cell transplantation setting to treat patients diagnosed with NY ESO-1 positive cancers.

Abstract: A method is provided for characterizing and/or prognosing prostate cancer in a subject comprising determining the expression level of at least one of CREM, ERRFI1, SRSF5, PDK4, HJURP, PDRG1, TRPM3, PDE4D, FI2, ADAMTS1, ADAMTS9, B3GNT5, CD38, CEBPD, CENPF, DKK1, EMP1, F3, IL1R1, IL8, JUNB, KLFIO, KLF4, LDLR, LGALS3, LPARI, MALAT1, MTUS1, MYBPC1, NFIL3, NR4A3, OAT, PI15, PTGS2, RHOBTB3, RIN2, RNFT2, SELE, SLC15A2, SOCS2, SOCS3, SSTR1, ST6GAL1, TSC22D1, XBP1 and ZFP36 in a sample from the subject. The method may be used to predict the likelihood of metastasis. Also disclosed are methods for diagnosing and selecting treatment for prostate cancer, together with corresponding methods of treatment. Systems, kits and computer programs for performing the methods are also provided.

Abstract: The present disclosure relates to chimeric post-transcriptional regulatory elements (PRE) and vectors useful for expressing a protein in a cell. The PRE contains alpha, beta and optionally gamma subelements selected from different native PRE sequences and are discovered to be more potent than their native counterparts.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a Group H nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention relates to a screening method for a drug target gene by using chemical-genetic profile compendium of the heterozygous deletion fission yeast strain and the comparative genetic analysis using the same. More precisely, the present inventors constructed the chemical-genetic profile compendium for drug candidates from the heterozygous deletion fission yeast strain of Schizosaccharomyces pombe (S. pombe), and then compared with the compendium with the chemical-genetic profile compendium of the budding yeast Saccharomyces cerevisiae (S. cerevisiae) in order to select efficiently drug target genes showing drug sensitivity. The screening method of the present invention can be efficiently used for the identification of a drug target gene in various eukaryotes because it facilitates the selection of a drug target gene showing sensitivity to the drug from the chemical-genetic profile compendium of the heterozygous deletion fission yeast strain.

Abstract: The invention relates to mammalian cells comprising at least one prokaryotic two-component signaling (TCS) pathway comprised of an activator protein A, a response regulator (RR) protein B activated by said protein A, such activation leading to an activated RR protein B, and an output gene C operably linked to a promoter. Transcription from said promoter is activated by activated RR protein B, and the expression of output gene C defines at least a first state (0, no transcription) and a second state (1, detectable transcription). The invention further relates to logic gates designed from such cells, and methods for integrating a plurality of output signals based on the cells and logic gates of the invention.

Abstract: A method for monitoring differentiation into cardiac muscle cells includes keeping, in an alive state, cells into which a reporter gene of luminescent protein configured to vary in luminescence intensity according to an expression of myocardial differentiation marker gene is introduced. The method includes acquiring a luminescence image as a still image by imaging light emitted from the cells in a light shielding state. The method includes acquiring sequential images with illuminating the cells. The method includes associating biological information obtained from the sequential images with biological information obtained from the still image.

Abstract: The present invention relates to the identification of pancreatic cancer biomarkers for the detection of early pancreatic cancer. The present invention also provides methods of diagnosing pancreatic cancer and distinguishing between pancreatic cancer and chronic pancreatitis. The present invention additionally provides kits that find use in the practice of the methods of the invention.

Abstract: The present disclosure describes improved adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia). Described are recombinant nucleic acid molecules, vectors and recombinant AAV that include a G6PC promoter/enhancer, a synthetic intron, a G6PC coding sequence (such as a wild-type or codon-optimized G6PC coding sequence), and stuffer nucleic acid sequence situated between the G6PC promoter/enhancer and the intron, as well as between the intron and the G6PC coding sequence. The recombinant AAVs disclosed herein exhibit highly efficient liver transduction and are capable of correcting metabolic abnormalities in an animal model of GSD-Ia.