Abstract: The present invention refers to an oligonucleotide comprising 12 to 25 nucleotides, wherein at least one of the nucleotides comprises a modification selected from the group consisting of a bridged nucleic acid such as LNA, ENA, a 2?Fluoro modified nucleotide, a 2 O-Methyl modified nucleotide, a 2 O-Methoxy modified nucleotide, a FANA and a combination thereof. The oligonucleotide hybridizes with a nucleic acid sequence of Foxp3 of SEQ ID NO. 1 and/or of SEQ ID NO. 2 resulting in a reduction of the expression of FoxP3 mRNA, FoxP3 pre-mRNA or a combination thereof. The invention is further directed to a pharmaceutical composition comprising an oligonucleotide of the present invention and to the oligonucleotide and pharmaceutical composition, respectively for use in a method of preventing and/or treating a disorder, where FoxP3 imbalance is involved.

Abstract: A recombinant NK-92 cell has a constitutive active promotor that effects expression of native CD16, and most preferably homogenous CD16 158V. Further contemplated recombinant NK-92 cells also include a recombinant nucleic acid that encodes an intracellularly retained interleukin (e.g., IL-2 or er-IL-2), wherein the recombinant NK-92 cell will secrete no more than 5,000 pg/mL IL-2 into a culture medium. The recombinant NK-92 cells presented herein have a significantly improved signal-to-noise ratio and exhibit reduced non-ADCC cytotoxicity.

Abstract: Described herein are antisense oligonucleotides, vectors, and related compositions and methods for increasing expression of PKD1 mRNA and Polycystin 1 protein and uses thereof for the treatment of autosomal dominant polycystic kidney disease (ADPKD).

Abstract: The technology described herein is directed to Aptamer and Ribozyme Equilibrium Shifting (ARES) regions, including ON-switches and OFF-switches, which can be harnessed to regulate the stability of RNA molecules. Also described herein are compositions comprising such RNA molecules and methods of using them to regulate translation of cargo polypeptides.

Abstract: The current invention relates to nucleic acid impurities in a composition comprising a parvoviral vector. In particular, the current invention shows that DNA impurities are not randomly encapsulated within a parvoviral virion. The invention therefore relates to a method for identifying and quantifying a nucleic acid impurity in a composition comprising a parvoviral vector. Finally, the current invention relates to method of determining whether a composition comprising a parvoviral vector is regarded as clinically pure.

Abstract: The present invention provides products, systems, and methods of cultivation of non-human metazoan cells.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids such as DNA. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

Abstract: In one aspect of the instant invention, lentiviral vectors are provided, particularly for treating hemoglobinopathies. Composition comprising the lentiviral vector are also encompassed by the instant invention. In accordance with another aspect of the instant invention, methods of inhibiting, treating, and/or preventing a hemoglobinopathy (e.g., sickle cell disease or thalassemia) in a subject are provided. In a particular embodiment, the method comprises administering a viral vector of the instant invention to a subject in need thereof hemoglobinopathy. In a particular embodiment, the subject has sickle cell anemia.

Abstract: The invention provides, inter alia, a nucleic acid (e.g. expression vector) that comprises at least a first coding sequence and a second coding sequence. Each coding sequence is under the control of an inducible promoter of defined strength. Different promoters can have different strengths. Each promoter is responsive to the same inducer. The invention also provides: methods of expressing coding regions, methods of making a product of a multi-enzyme pathway, and methods of optimizing the yield of a product of a multi-enzyme metabolic pathway using the nucleic acids provided by the invention. Also disclosed is a method of non-enzymatic gene cloning useful for practicing the invention.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The present invention relates to new aptamer molecules for use in the treatment and/or diagnosis of autoimmune diseases associated with autoantibodies against G-protein coupled receptors, a pharmaceutical composition comprising such aptamer molecules, an apheresis column comprising such aptamer molecules and a method for the determination of nucleotide sequences for use as sequences of aptamer molecules.

Abstract: Synthetic RNA molecules comprising at least two RNA-binding protein (RBP)-binding motifs, wherein the at least two RBP-binding motifs bind the same first RBP and comprise non-identical sequences are provided. Synthetic RNA molecules comprising an RBP-binding motif that binds two orthogonal RBPs, comprising at least three RBP-binding motifs for three orthogonal RBPs or comprising a first RBP-binding motif, a second RBP-binding motif, a regulatory element and an open reading frame wherein the first and second RBP-binding motifs cooperatively enhance translation of the open reading frame are also provided. Compositions, cells and methods of use or generating the synthetic RNA molecules are also provided.

Abstract: Provided are oligomeric compounds, methods, and pharmaceutical compositions for reducing the amount or activity of PLN RNA in a cell or animal, and in certain instances reducing the amount of phospholamban protein in a cell or animal. Such oligomeric compounds, methods, and pharmaceutical compositions are useful to treat cardiomyopathy, heart failure, or arrhythmia.

Abstract: The disclosure provides a versatile method termed CRISPR-SKIP that utilizes cytidine and/or adenine deaminase base editors to program exon skipping by mutating target DNA bases within splice acceptor sites and/or splice enhancer sites. Given its simplicity and precision, CRISPR-SKIP will be broadly applicable in gene therapy and synthetic biology.

Abstract: Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guide nucleic acid (gRNA), which are useful in the repression of a proprotein convertase subtilisin/kexin Type 9 (PCSK9) gene. Also provided are methods of using such systems to repress transcription of PCSK9.

Abstract: The present invention relates to a method for recording a transcriptome of a cell by: providing a test cell that includes a first transgene nucleic acid sequence encoding a fusion protein that is a reverse transcriptase polypeptide and a Cas1 polypeptide and a second transgene nucleic acid sequence encoding a Cas2 polypeptide, wherein the first transgene nucleic acid sequence and the second transgene nucleic acid sequence are under transcriptional control of an inducible promoter sequence, and a third transgene nucleic acid sequence including a CRISPR direct repeat (DR) sequence; wherein the CRISPR direct repeat sequence is specifically recognizable by a RT-Cas1-Cas2 complex formed by the expression products of the first transgene nucleic acid sequence and the second transgene nucleic acid sequence.

Abstract: Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for a target biomolecule and the miRNA can cause the target mRNA to be degraded or inactivated, decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a complement or a factor. In some embodiments of the present disclosure, the target biomolecule is a complement such as complement C1q, complement C1r, complement C1s, complement C3 or complement C5. In some embodiments of the present disclosure, the target biomolecule is a factor such as Factor B, Factor D or Factor 10.

Abstract: Described herein are synthetic promoters and/or enhancers that are specific for cancer cells and methods of engineering synthetic cancer-specific promoters.

Abstract: Present invention relates to the in vitro use of the level or concentration in a salivary or breath sample of bacteria belonging to the Alloprevotella, Prevotella, Campylobacter, Rothia, Catonella, Porphyromona, Fretibacterium genus, or any combination thereof, for the diagnosis of carcinomas or epidermoid cancers, especially epidermoid cancer of the head and neck, in a patient, or to obtain useful data that allow such a diagnosis.