Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: This disclosure provides engineered microbes coding at least one rare earth element (REE) binding ligand for the preferential separation of REEs, as well as methods of use thereof.

Abstract: Disclosed are methods of making a genetically cell that expressed FOXP3 and methods of treatment. In some embodiments, the method can providing a first nucleotide sequence, wherein the first nucleotide sequence comprises a coding strand, the coding strand comprising one or more regulatory elements and a FOXP3 gene or portion thereof providing a nuclease and performing a gene editing process on the first nucleotide sequence, which edits said one or more regulatory elements, and optionally edits the FOXP3 gene or portion thereof. Methods of treating a subject suffering from an autoimmune disease and subjects suffering the effects of organ transplantation are also provided.

Abstract: The present invention relates to a method of modifying at least one gene in a cell via CRISPR/Cas, wherein the at least one gene has at least three alleles. The present invention further relates to cells obtainable by the method of the invention. Additionally, the present invention provides a method of producing a protein in a cell obtainable by the method of modifying at least one gene of the invention. Moreover, the invention relates to proteins obtainable by the method of producing a protein and use thereof, for example in therapy.

Abstract: Described herein is a method for treating Alzheimer's disease (AD) by selective silencing of the amyloid precursor protein (APP) using Cas9 nuclease gene editing. Methods of making and using genetic constructs comprising a Cas9 nuclease and a sequence encoding guide RNA (gRNA) specific to APP capable of truncating the C-terminus of APP, as well as compositions comprising these constructs, are provided.

Abstract: Disclosed herein are polynucleotides encoding ligand-inducible gene switch polypeptides, and systems comprising gene switch polypeptides for modulating the expression of a heterologous gene and an interleukin in a host cell. The compositions, methods and systems described herein facilitate ligand dependent expression of polypeptides including but not limited to cytokines and antigen binding polypeptides.

Abstract: The invention relates to a method for producing a ribonucleic acid (RNA) molecule composition comprising n different RNA molecule species, the method comprising a step of RNA in vitro transcription of a mixture of m different deoxyribonucleic acid (DNA) molecule species in a single reaction vessel in parallel, i.e. simultaneously, and a step of obtaining the RNA molecule composition. Also provided is the RNA composition provided by the inventive method and a pharmaceutical composition comprising the same as well as a pharmaceutical container. Moreover, the invention provides the RNA composition and the pharmaceutical composition for use as medicament.

Abstract: A method of making a polypeptide including one or more D-amino acids is provided. The method includes combining a ribosome with protein translation factors including (1) a template encoding the polypeptide, wherein the template encoding the polypeptide includes one or more codons which have been recoded to accept a tRNA attached to a D-amino acid, (2) a plurality of L-amino acids and a plurality of corresponding tRNAs, (3) a plurality of D-amino acids and their corresponding aminoacyl tRNA synthetase or a plurality of tRNAs ligated with a D-amino acid, and (4) elongation factor P in a concentration of 2 to 20 micromolar, wherein translation of the template encoding the polypeptide occurs to produce the polypeptide including one or more D-amino acids.

Abstract: The present disclosure provides a sphere-packing lattice electroporation device configured for use as a stand-alone unit or in an automated multi-module cell processing environment and configured to decrease cell processing time and cell survival. The sphere-packing lattice utilizes lattice-forming beads that are uniform in size and that self-assemble into a crystalline-like lattice.

Abstract: The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.

Abstract: The present invention relates to the field of genetic engineering, preferably the expression of recombinant proteins (RP). In particular, the invention relates to a promoter and variants thereof having an equal function and more than 90% sequence identity. The promoter comprises a fragment of 1147 base pairs (bp) of a first promoter, promoter of the ?-actin gene of the Cricetulus griseus genome, enriched in cytosine-guanine dinucleotides (RegCG). The first promoter can be upstream of a second promoter, cytomegalovirus (CMV) promoter. The invention also relates to vectors, transfected cellular lines and a method for producing RP in mammal cells that have been transfected with vectors containing said promoter or variants thereof.

Abstract: The present invention discloses a process for the secretion of brazzein in improved yield.

Abstract: The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.

Abstract: The application provides improved methods of genome editing. The genome editing systems described herein comprise a RNA-guided nuclease molecule and a Repair-Modulating Enzyme Molecule (RMEM).

Abstract: The invention provides nucleic acids and nucleic acid expression vectors containing optimized mGluR6 promoters for expression of transgenes in the retina. The compositions and methods of the invention are useful for expression of gene products to preserve, improve, or restore phototransduction or vision.

Abstract: The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.

Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.

Abstract: The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

Abstract: The present disclosure provides novel bacterial strains with altered expression or start codon modification of one or more RNA degradation/processing genes. The RNA degradation genes of the present disclosure are controlled by heterologous promoters. The present disclosure further describes methods for generating microbial strains comprising heterologous promoter sequences operably linked to RNA degradation/processing genes.