Abstract: The specification describes a composition comprising an improved eukaryotic cell culture medium, which can be used for the production of a protein of interest. TaXULne can be added to the serum-free media or chemically-defined media to increase the production of a protein of interest. Methods for recombinantly expressing high levels of protein using the media compositions are included.

Abstract: The specification describes a composition comprising an improved eukaryotic cell culture medium, which can be used for the production of a protein of interest. TaXULne can be added to the serum-free media or chemically-defined media to increase the production of a protein of interest. Methods for recombinantly expressing high levels of protein using the media compositions are included.

Abstract: The present disclosure provides a method of treating a human patient comprising the steps of: systematically administering multiple doses of a parenteral formulation of a replication capable oncolytic adenovirus of subgroup B in a single treatment cycle, wherein the total dose given in each dose is in the range of 1×1010 to 1×1014 viral particles, and wherein each dose of virus is administered over a period of 1 to 90 minutes, for example at a rate of viral particle delivery in the range of 2×1010 particles per minute to 2×1012 particles per minute. The disclosure further extends to formulations of the oncolytic adenoviruses and combination therapies of the viruses and formulations with other therapeutic agents.

Abstract: Combinations comprising one or more nucleic acid molecules comprising a nucleic acid sequence A encoding for a TCR alpha chain linked to a dimerization domain, and a nucleic acid sequence B encoding for a TCR beta chain linked to a dimerization domain, as well as proteins encoded by such nucleic acid molecules and corresponding uses and methods.

Abstract: The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin and comprises an open reading frame encoding a reprogramming factor. Such RNA replicons are useful for expressing a reprogramming factor in a cell, in particular a somatic cell. Cells engineered to express such reprogramming factors are useful in cell transplantation therapies.

Abstract: The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.

Abstract: Provided herein, in some aspects, are methods for preventing or treating diabetes in a subject, the method comprising assaying a genomic sample obtained from the subject for an intergenic variant located in a region between a C2 calcium-dependent domain containing 4A gene (C2CD4A) and a C2 calcium-dependent domain containing 4B gene (C2CD4B), and when the intergenic variant is present in the genomic sample, administering to the subject a therapy for diabetes. Also provided herein are rodent cells homozygous for a C2cd4a mutation and/or homozygous for a C2cd4h mutation, and methods for producing the rodent cells.

Abstract: Compositions of polynucleotide(s), pharmaceutical compositions thereof, and methods of use thereof are disclosed. A polynucleotide may encode for a cystic fibrosis transmembrane conductance regulator (CFTR) protein or a functional fragment thereof. The polynucleotide may be assembled with a lipid composition for targeted delivery to a cell or an organ, such as a lung cell or a lung of a subject. Methods for enhancing an expression or activity of CFTR protein in a cell are provided. Methods for treating a subject having or suspected of having a CFTR-associated condition are also provided.

Abstract: Corneal stromal scars are the leading cause of corneal blindness. The present invention relates to methods and compositions useful in therapies for this pathological condition. The invention provides corneal stromal stem cells and certain other stem cells and as well as exosome polynucleotides produced by such cells, and methods for making and using these cells and compositions. The invention is based upon the discovery that exosomes and their associate active components obtained from these cells comprise agents having the same capacity as corneal stromal stem cells to reduce scarring and prevent scar formation in patients having corneal damage.

Abstract: Compositions and methods for eradicating tumor cells using novel compositions are contemplated. In one aspect, a pharmaceutical composition comprising a CAR scaffold and an antigen binding domain in a single chimeric species is provided. In some aspects, the CAR scaffold may comprise a CD28 costimulatory signaling region and a CD3? activation domain or a complete CD3? activation domain. In some aspects, the CAR scaffold may be codon-optimized for improved expression in mammalian cell lines and/or for improved function upon transfection into natural killer (NK) or other immune cells. In further aspects, the antigen binding domain may comprise a VL and VH domain linked by a spacer and may be codon optimized. A CD64 leader sequence may be attached to the antigen binding domain, e.g., at the N-terminus of the antigen binding domain.

Abstract: The invention relates to a composition for inducing a T cell mediated immune response for the treatment or prevention of prostate cancer comprising a modified Vaccinia virus Ankara (MVA) vector expressing the 5T4 antigen polypeptide under control of a poxvirus F11 promoter. Suitably said poxvirus F11 promoter is the endogenous MVA F11 promoter. More suitably said vector expresses a polypeptide having the amino acid sequence of SEQ ID NO: 1 or said vector expresses a polypeptide encoded by a polynucleotide having the nucleic acid sequence of SEQ. ID NO: 2. The invention also relates to uses and methods.

Abstract: Provided herein are improved rAAV (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of ocular disorders or CNS disorders wherein the rAAV comprise one or more substitutions of amino acids that interact with heparan sulfate proteoglycan. The invention provides methods for improved transduction of retinal cells and methods for treating ocular diseases with improved compositions of rAAV particles. Further provided herein are improved recombinant adeno-associated virus (rAAV) (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of disorders of the CNS. The invention provides methods for delivering the rAAV to the CNS, methods for treating disorders of the CNS with improved compositions of rAAV particles, and kits for delivering the rAAV to the CNS and/or treating a CNS disorder.

Abstract: The specification describes a composition comprising an improved eukaryotic cell culture medium, which can be used for the production of a protein of interest. TaXULne can be added to the serum-free media or chemically-defined media to increase the production of a protein of interest. Methods for recombinantly expressing high levels of protein using the media compositions are included.

Abstract: The systems and methods are directed to leveraging the channel geometry and configuration to overcome diffusion limitations of current transduction systems. The methods may include a method of transducing target cells using a device. The device may include at least one continuous channel. The method may include delivering target cells and viral vectors into a transduction region of the channel. After transducing for some incubation time, a flushing solution may be delivered. The method may include collecting transduced cells after the transducing incubation time and the delivering of the flushing solution.

Abstract: A highly effective technique for fertilizing an oocyte with a sperm cell to produce a zygote can be carried out in a bioreactor and the zygote can optionally be cultured in the bioreactor into a blastocyst stage embryo for implantation into the uterus of a female recipient. The success rate and probability of fertilization is enhanced by operating the bioreactor reactor under conditions of inter-galactic motion which increases the probability of the sperm coming in close proximity to and fertilizing the oocyte. This method involves the steps of collecting an oocyte from a female donor, collecting sperm from a male donor, fertilizing the oocyte with the sperm in a rotating bioreactor to produce a zygote, culturing the zygote into a blastocyst stage embryo, and implanting the blastocyst stage embryo into a uterus of a recipient female.

Abstract: A product comprising two or more artificial transcription repressors (ATRs), or polynucleotides encoding therefor, selected from groups (a), (b), (c) or (d): (a) an ATR comprising a DNA-binding domain operably linked to a KRAB domain or homologue thereof; (b) an ATR comprising a DNA-binding domain operably linked to a DNMT3A, DNMT3B or DNMT1 domain or homologue thereof; (c) an ATR comprising a DNA-binding domain operably linked to a DNMT3L domain or homologue thereof; and (d) an ATR comprising a DNA-binding domain operably linked to a SETDB1 domain or homologue thereof, wherein at least two of the ATRs are selected from different groups (a), (b), (c) or (d).

Abstract: 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 sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for a target biomolecule and the miRNA can cause a decrease in 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 dopamine receptor. In some embodiments of the present disclosure, the target biomolecule is a dopamine receptor such as the D1 dopamine receptor, such as the D2 dopamine receptor, such as the D3 dopamine receptor, or such as the D4 dopamine receptor.

Abstract: Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.

Abstract: The present invention provides a novel liposome composition containing eribulin or its pharmacologically permissible salt, and its method of manufacture.

Abstract: SnRNA systems comprising engineered stem loops are disclosed herein.