Abstract: Described herein are synonymously altered gene sequences which express protein in differing levels within secretory as compared to non-secretory target tissue. An expression cassette comprising an open reading frame (ORF) for a protein under the control of regulatory sequences which direct expression of the product in cell, which ORF has been modified to preferentially increase expression levels in a selected tissue, wherein the modified ORF is characterized by a triplet frequency of any one of Tables 3-12, 16 or 17.

Abstract: The invention provides compositions and methods for the detection of small RNA molecules in a multiplexed reaction. The assays and kits described herein are applicable for the identification, diagnosing, and monitoring of disorders including, but not limited to cancer, developmental and degenerative disease, neurological disorders, and stem cell disorders.

Abstract: Methods for diagnosis and surveillance of complex multi-factorial disorders such as cancer by screening of easily accessible biomarkers are disclosed. Highly stable cell free Circulating Nucleic Acids (CNA) present as both RNA and DNA species have been discovered in the blood and plasma of humans. Correlations between tumor-associated genomic/epigenetic/transcriptional changes and alterations in CNA levels are strong predictors of the utility of this biomarker class as clinical indicators. Methods for using microRNAs (miRNAs) representing a class of naturally occurring small non-coding RNAs of 19-25 nt as markers that can associate their specific expression profiles with cancer development are disclosed. Methods for isolating plasma fractions for the study of miRNA biomarkers and for measurement of circulating miRNA levels are disclosed.

Abstract: Disclosed herein are methods and systems for the concentration of cells from a cell suspension into unprocessed tissue, such as adipose tissue. Also disclosed herein are systems for optimizing hydration of tissue and cell enriched grafts.

Abstract: Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

Abstract: The invention relates to a method for analyzing a genomic region of an organism, comprising four major parts. The first part involves the isolation of mRNA from a selected organism that is used for the preparation of small single stranded DNA fragments with one adaptor containing an affinity label. These DNA fragments are used in part three. In the second part, genomic DNA from the same or a related organism is isolated. This genomic DNA is fragmented and ligated to adaptor molecules. In the third part, these genomic fragments are hybridized with single stranded DNA fragments from part one, and the hybrids formed in this process are used for synthesis of DNA fragments. These fragments will be used in part four which involves sequencing of these fragments using one of the available high throughput sequencing methods.

Abstract: Compositions and methods for genetically modifying the production levels of nicotine and other alkaloids in plants are provided.

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 method comprises: (a) isolating a sample from the breast tumor; (b) determining the level of expression of GRP94, FN14 or both in the sample, and (c) comparing said level with the level of said gene(s) in a control sample, wherein if it is detected an overexpression of said gene(s), in respect of the control sample, it is indicative of the risk for developing brain metastasis. The kit to carry out the method of the invention comprises appropriate means to determine the level of expression of each one of the markers. Both, the method and kit provides accurate information about the risk of developing brain metastasis in an early state, which can lead to a reduction of the incidence of breast cancer brain metastasis.

Abstract: The invention provides a method for detecting a target nucleotide sequence by tagging the nucleotide sequence with a nucleotide tag, providing a probe oligonucleotide with a melting temperature Tm1, comprising a regulatory sequence and a nucleotide tag recognition sequence; incorporating the probe oligonucleotide into the tagged polynucleotide in a polynucleotide amplification reaction, providing a regulatory oligonucleotide with a melting temperature Tm2, comprising a sequence segment that complementary to the regulatory sequence and a tail segment that does not hybridize to the probe nucleotide when the sequence segment and the regulatory sequence are annealed, amplifying the tagged target nucleic acid sequence in a PCR amplification reaction using the probe oligonucleotide as a primer, and using a DNA polymerase with high strand displacement activity and low 5?-nuclease activity, and detecting the amplification product; wherein Tm1 and Tm2 are higher than the annealing temperature associated with the polyn

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.

Abstract: Disclosed are genetic expression cassettes, and vectors comprising them useful for the delivery of isolated nucleic acid segments including those expressing or encoding one or more selected therapeutic constructs (including, without limitation, therapeutic peptides, polypeptides, ribozymes, or catalytic RNA molecules), to one or more selected cells or tissues of a vertebrate animal. Methods employing the disclosed genetic constructs in the development of gene therapy-based viral vector systems are also disclosed. The expression cassettes and viral vectors disclosed herein provide new tools for methods of treating mammalian, and in particular, human diseases, disorders, and/or dysfunctions. The disclosed compositions and methods find particular utility in a variety of investigative, diagnostic, and therapeutic regimens, including, for example, in the treatment or amelioration of symptoms of a variety of mammalian, and particularly, human conditions.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.

Abstract: The present invention relates to an improved process for the preparation of unsaturated fatty acids and to a process for the preparation of triglycerides with an increased content of unsaturated fatty acids. The invention relates to the generation of transgenic microorganism, with an increased content of fatty acids, oils or lipids with ?6 double bonds owing to the expression of a moss ?6-desaturase. The invention furthermore relates to transgenic organisms comprising a ?6-desaturase gene, and to the use of unsaturated fatty acids ort of the triglycerides with an increased content if unsaturated fatty acids prepared in the process.

Abstract: The invention provides a method for detecting a target nucleotide sequence by tagging the nucleotide sequence with a nucleotide tag, providing a probe oligonucleotide with a melting temperature Tm1, comprising a regulatory sequence and a nucleotide tag recognition sequence; incorporating the probe oligonucleotide into the tagged polynucleotide in a polynucleotide amplification reaction, providing a regulatory oligonucleotide with a melting temperature Tm2, comprising a sequence segment that is at least partially complementary to the regulatory sequence, amplifying the tagged target nucleic acid sequence in a PCR amplification reaction using the probe oligonucleotide as a primer, and detecting the amplification product; wherein Tm1 and Tm2 are higher than the annealing temperature associated with the polynucleotide amplification reaction.

Abstract: Provided herein are methods of determining the aggressiveness or indolence of a ductal carcinoma in situ lesion. Also provided are methods of development treatment plans for subjects with a ductal carcinoma in situ lesion based on the aggressiveness of the lesion.

Abstract: The present invention relates to improved methods for the production of viral particles, viral vector particles and recombinant proteins. In particular, the invention relates to improved methods for the production of recombinant polyomaviral vector particles and polyomaviral vector production cell lines. More in particular, the invention relates to methods for the production of simian polyomaviral vector particles such as simian virus 40 (SV40) viral vector particles. The invention also relates to compositions comprising viral vectors and uses thereof and viral vector particles to treat genetic disorders, transplant rejection, autoimmune diseases, infectious diseases, allergies or cancer. The invention also relates to methods for the production of recombinant proteins in mammalian cells and methods to enhance the production of recombinant proteins in mammalian cells.

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: Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

Abstract: Disclosed herein is the identification of a new therapeutic target, an upstream target, the microtubule-organizing center (MTOC), for arresting mitosis and inhibiting cell growth and proliferation. Achieving mitotic arrest involves the interaction of two proteins with the ?TuRC of the MTOC: Kinesin-14 or a Tail peptide of Kinesin-14 having the amino acid sequence of SEQ ID NO: 1 and an antagonist capable of disarming the function of the BimC domain of Kinesin-5. Methods and compositions for screening for Kinesin-5 BimC antagonists are also disclosed.