Abstract: The present invention relates to methods and kits for detection protein-protein interactions.

Abstract: The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Abstract: An object of the present invention is to provide a method of producing a peptide containing a charged non-proteinogenic amino acid in a cell-free translation system, and the like. The present invention provides a method of producing a peptide containing a charged non-proteinogenic amino acid. It includes a step of expressing a peptide in a cell-free translation system including (i) at least one tRNA to which a non-proteinogenic amino acid having a protecting-group-introduced charged group has been bound and (ii) a nucleic acid that encodes the peptide and contains at least one codon corresponding to an anticodon of the tRNA; and a step of removing the protecting group of the non-proteinogenic amino acid residue contained in the peptide.

Abstract: The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

Abstract: The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

Abstract: Disclosed herein are methods of producing chondrocytes from pluripotent stem cells. The invention further provides methods of regenerating cartilaginous tissue.

Abstract: The present disclosure relates to recombinantly engineered cells that contain a chlorite dismutase polypeptide and methods for culturing such cells in a culture medium containing chlorite in an amount sufficient to reduce the growth rate or kill contaminating microorganisms without killing the recombinantly engineered cells. Also provided are methods for the production of a fermentation product using the recombinantly engineered cells.

Abstract: The present disclosure is directed to methods and compositions for inhibiting a cancer cell using nucleic acid sequences encoding elephant p53 or elephant p53 amino acid sequences.

Abstract: Methods of making mutant Cas9 proteins are described.

Abstract: Anti-cytokine therapy has revolutionized immunological disease treatment, but is not always effective and subject to treatment resistance as the cytokine cascade is highly redundant and multiple cytokines are involved in inflammation. Targeting a critical common regulator of inflammatory effectors is desirable. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) is a master regulator of multiple genes important for inflammation. Subcellular localization shows that LRBA translocated to the nucleus upon LPS stimulation and colocalized with multiple proteins associated with the endosome membrane system, indicating a critical role in membrane/vesicle trafficking essential for deposition, secretion and signal transduction of immune effectors.

Abstract: The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies of humans. More specifically, the present invention relates to oncolytic adenoviral vectors alone or together with therapeutic compositions for therapeutic uses and therapeutic methods for cancer. In one aspect the present invention relates to separate administration of adoptive cell therapeutic composition and oncolytic adenoviral vectors. Furthermore, the present invention relates to a pharmaceutical kit and a pharmaceutical composition, both utilizing oncolytic adenoviral vectors.

Abstract: The present invention provides liposomes comprising a lipid bilayer and a polymer-conjugated lipid, wherein said polymer-conjugated lipid is incorporated into said lipid bilayer. The present invention also provides methods of producing the liposomes as well as a method of delivering a nucleic acid to a subject comprising the step of administering said nucleic acid encapsulated in a mixed liposome, a method for performing diagnostic imaging in a subject, comprising the step of administering a diagnostic agent encapsulated in a mixed liposome, and methods for treating, inhibiting, or suppressing a pathological condition in a subject comprising administering to said subject a mixed liposome.

Abstract: Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

Abstract: There are provided liposomes, comprising cationic lipids, a membrane stabilizing lipid and at least one lipid conjugated to a polyethylene glycol (PEG) derivative, in particular PEG-amine, the liposomes are coated with a glycosaminoglycan, in particular, Hyaluronic Acid (HA), compositions comprising the same, methods for their preparation and uses thereof for the efficient delivery of nucleic acids, such as, si RNA molecules and for treating various conditions, such as cancer.

Abstract: The present disclosure provides compositions and methods of site-specific modification of a target DNA, or a protein associated with a target DNA, in a eukaryotic cell. The present disclosure provides methods of binding a target DNA in a eukaryotic cell.

Abstract: Methods are provided for the use of Cas9 in genome engineering of stem cells. Methods include introducing into the stem cell a first foreign nucleic acid encoding a guide RNA complementary to a target DNA and which guides a Cas9 enzyme to the target DNA, wherein the RNA and the enzyme are members of a co-localization complex for the target DNA, introducing into the stem cell a second foreign nucleic acid encoding a donor nucleic acid sequence, wherein the guide RNA and the donor nucleic acid sequences are expressed, wherein the guide RNA and the Cas 9 enzyme co-localize to the target DNA, the Cas 9 enzyme cleaves the target DNA and the donor nucleic acid is inserted into the target DNA to produce altered DNA in the stem cell.

Abstract: Methods for inhibiting oligonucleotide activity in vitro or in vivo to a cell that are formulated with at least one oligonucleotide encapsulated in a lipid nanoparticle are disclosed.

Abstract: The present disclosure provides opsins, including variant opsins with increased activity and/or increased trafficking to the plasma membrane. The opsins are useful in therapeutic and screening applications, which are also provided.

Abstract: A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

Abstract: The present invention provides an attenuated African Swine Fever (ASF) virus which lacks a functional version of the following genes: multigene-family 360 genes 9L, 10L, 11L, 12L, 13L and 14L; and multigene-family 505 genes 1R, 2R, 3R and 4R. The invention further provides an attenuated African Swine Fever (ASF) virus which lacks a functional version of the DP148R gene. The present invention also provides a vaccine comprising such an attenuated virus and its use to prevent ASF. Further, the invention relates to intranasal administration of an attenuated ASF virus.

Abstract: The present invention provides methods and compositions for improving the efficacy of viral transduction of cells. More particularly, the present invention provides methods and materials useful for safely and reliably improving the efficiency of methods for transducing cells, such as human hematopoietic stem cells (HSC), with viruses and/or viral vectors. The compositions and methods are useful for therapeutic indications amenable to treatment with hematopoietic stem cell gene therapies.

Abstract: The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.

Abstract: A method for performing homologous recombination between at least a first nucleic acid molecule and a second nucleic acid molecule which share at least one region of sequence homology. A method for improving the efficiency of homologous recombination.

Abstract: Chimeric antigen receptors containing ROR1 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: Provided herein are methods to characterize preparations of recombinant viral particles using analytical ultracentrifugation. Recombinant viral particles include recombinant adeno-associated viral particles, recombinant adenoviral particles, recombinant lentiviral particles and recombinant herpes simplex virus particles. Variant species of recombinant viral particles including empty capsids and recombinant viral particles with variant genomes (e.g., truncated genomes, aggregates, recombinants) can be identified and quantitated. The methods can be used to characterize preparations of recombinant viral particles regardless of the sequence of the recombinant viral genome or the serotype of the recombinant viral capsid.

Abstract: The present invention is directed to nucleic acid and amino acid sequences of a novel piggyBac transposase enzymes created by modifying the transposase of Trichoplusia ni. The piggyBac transposases of the present invention are functionally active or hyperactive for excision and have decreased integration activity compared to wild type Trichoplusia ni piggyBac transposase enzyme. These transposases are ideal for use in methods of transforming cells and organisms. In particular embodiments, the present invention provides methods of transient integration and expression of transgenes.

Abstract: The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) “off-the-shelf” T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.

Abstract: The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

Abstract: Disclosed herein are tissue-based drain manifolds comprising partially or completely decellularized tissue that has been processed to form tubes, columns, sheets, or other shapes and which are useful for managing the drainage of fluid and/or the administration of negative pressure at an implant site in a patient. The manifolds can be implanted in a patient and provide a natural scaffold in which native cells from surrounding tissue can migrate and proliferate, thereby avoiding the need to remove the implanted manifolds after drainage is complete.

Abstract: A platform for ex vivo isolation, production, and formulation of genetically-modified cells is described. The platform utilizes a software-enabled point-of-care and/or portable device making gene therapy more widely available.

Abstract: The invention provides means and methods for modulating the occurrence of somatic hypermutations in antibody producing plasmablast-like B-cells.

Abstract: A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.

Abstract: Problem To provide a chiral nucleic acid adjuvant and anti-allergic agent having anti-allergic effect. Solution An adjuvant which comprises oligonucleotides which comprise two to four CpG motifs each represented by 5?-X1CpGX2-3? and has a length of 14 to 32 nucleotides, wherein a nucleic acid at 3? end side of at least two CpG motifs is connected by phosphorothioate linkage, wherein each nucleic acids at 3? end and 5? end of the oligonucleotide is S type nucleic acids connected by phosphorothioate linkage, and wherein the oligonucleotide comprises at least one nucleic acid without phosphorothioate modification. The present invention relates to an adjuvant comprising the oligonucleotide represented by the sequence number 67. The present invention relates to an anti-allergic agent comprising these adjuvant.

Abstract: The present invention relates to transposase adapters and uses thereof, including uses in preparing DNA molecules, in vitro amplification, sequencing of nucleic acids, and screening of DNA libraries for sequences of interest as well as nucleic acid delivery.

Abstract: The present invention provides for compositions and methods for modulating hematopoetic stem cell populations by using HCS modulators, which are agents that either increase HSC numbers or decrease HSC numbers as desired by a particular indication. For example, HSC modulators found to increase HSC numbers include prostaglandin E2 (PGE2) and agents that stimulate the PGE2 pathway. Conversely, HSC modulators that prevent PGE2 synthesis decrease HSC numbers. HCS modulators may be used in vitro, in vivo, or ex vivo.

Abstract: The present invention provides for compositions and methods for modulating hematopoetic stem cell populations by using HCS modulators, which are agents that either increase HSC numbers or decrease HSC numbers as desired by a particular indication. For example, HSC modulators found to increase HSC numbers include prostaglandin E2 (PGE2) and agents that stimulate the PGE2 pathway. Conversely, HSC modulators that prevent PGE2 synthesis decrease HSC numbers. HCS modulators may be used in vitro, in vivo, or ex vivo.

Abstract: The present invention concerns the use of methods for evaluating ?-adrenergic receptor targeting agent treatment for a patient, particularly one with a heart condition. In general, the disclosed methods entail determining the presence or absence of one or more polymorphisms in an endothelin gene system member. Based on the results of this determination, a ?-adrenergic receptor targeting agent may be prescribed, administered or a treatment regimen altered, including the administration of a ?-blocker. Accordingly, methods of treatment are also described.

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: The invention provides methods, compositions and kits for the identification and enrichment of progenitor cell lines obtained from pluripotent stem cells.

Abstract: Aspects of the disclosure include devices, systems and methods for optogenetic modulation of action potentials in target cells. The subject devices include light-generating devices, control devices, and delivery devices for delivering vectors to target cells. The subject systems include light-activated proteins, response proteins, nucleic acids comprising nucleotide sequences encoding these proteins, as well as expression systems that facilitate expression of these proteins in target cells. Also provided are methods of using the subject devices and systems to optogenetically inhibit and intercept action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or non-human animal subject.

Abstract: Methods of preparing platelet-rich plasma (PRP) compositions are disclosed which include adding CD34+ cells to the PRP composition. In addition, the concentration of stromal-derived factor-1 (SDF-1) in the PRP composition may be adjusted to a pre-determined value. The compositions may have elevated levels of white blood cells but reduced levels of neutrophils. Compositions produced by the method are also disclosed.

Abstract: The present invention concerns nanoparticle formulations suitable for the delivery of one or more therapeutic agents, the formulations comprising: a cationic cholesterol derivative; a neutral phospholipid; cholesterol or a neutral cholesterol derivative; and a saturated fatty acid, PEGylated neutral derivative of phosphatidylethanolamine or phosphatidylcholine.

Abstract: Disclosed are a recombinant expression vector and a host cell that contains the vector.

Abstract: A blade tip-provided micropipette holding apparatus has a tubular micropipette holder so constructed that a blade tip-provided micropipette to be inserted into a living cell can be mounted on a front-end portion thereof and a holder-holding device for holding the micropipette holder. The holder-holding device has a base member and a tubular rotating member which is rotatably held by the base member and into which the tubular micropipette holder can be penetrated. The tubular rotating member has holder position adjusting mechanisms each composed of a plurality of side holes formed on a side surface of the tubular rotating member at different positions of the side surface thereof in a circumferential direction thereof and holder position adjusting members each capable of entering into the tubular rotating member from the side holes and contacting an outer surface of the micropipette holder penetrating through the tubular rotating member.

Abstract: In certain embodiments, the disclosure relates to compositions and methods relating to a translation-based gene regulation system that functions in mammalian cells. In certain specific embodiments, the disclosure relates to methods of regulating gene expression via modulating translation termination.

Abstract: This application relates to a method for differentiating pluripotent stem cells (PSCs) into multi-competent renal precursor cells expressing Six2. These renal precursor cells are able to differentiate into fully functional and fully differentiated podocytes. Moreover this application relates to a method for differentiating human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into defined renal precursor cells expressing Six2 and podocytes based on linked steps of chemically defined medium inductions.

Abstract: Methods for the efficient isolation and use of pluripotent adipose-derived stem cells (PASCs) are provided. In certain embodiments the methods involve providing an adipose tissue sample from which the stromal vascular fraction is co-cultured with the adipocyte fraction. PASCs can be isolated with a high degree of purification without requiring an additional cell enrichment process (e.g. cell sorting). PASCs and their conditioned media can be used for tissue regeneration within hours of harvesting the adipose tissue, and without requiring cell expansion. PASCs can grow as floating individual cells, as clusters of cells, or attached to surface(s) of the culture vessel. PASCs do not produce teratomas in vivo, nor do they induce immunorejection upon transplantation, and they achieve a high efficiency in grafting. The cells and compositions can be used for cell therapy and to screen new drugs.

Abstract: The present invention provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to immunoresponsive cells bearing antigen receptors, which can be chimeric antigen receptors (CARS), which express introduced ligands for immunomodulatory molecules. In particular embodiments, engineered immunoresponsive cells are antigen-directed and resist immunosuppression and/or have enhances immune-activating properties.

Abstract: Provided herein are novel synthetic short hairpin RNA (shRNA) molecules and compositions and kits comprising such molecules, as well as methods of making and using these molecules, compositions, and kits.

Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.