Abstract: The present disclosure relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present disclosure relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present disclosure can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

Abstract: The present disclosure concerns a cell or tissue culture system comprising a solid support for the culture of adherent cells or adherent tissues and a plurality of cationic dendrimers associated to the surface of the solid support. Each cationic dendrimer includes one or more functional amine group. The cationic dendrimer is protonated at physiological pH. The cell or tissue culture system can be used for the culture of adherent cells or tissues and be used for the differentiation of stem cells.

Abstract: The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component.

Abstract: Crosslinking molecules that permit efficient identification of specifically associated proteins and the sites of crosslinking in biological or other samples include two cleavable bonds that are cleavable under the same conditions as peptide bonds in mass spectrometric determinations. Sets of the invention crosslinkers may be provided with isobaric labels containing reporter ions of differing molecular weights to permit relative quantitation of crosslinked protein pairs.

Abstract: Homogeneous human amniotic fluid stem cell clones are provided. The clones serve as direct bioassays to test the effect of drugs, nutraceuticals, vitamins and toxic agents on fetus growth, differentiation and development, and may be administered in form of pharmaceutical compositions for reconstructive engineering and for the treatment of cardiac, neurological and osteoarthritic diseases.

Abstract: Disclosed herein are antigenic peptide-MHC molecules, termed comPACTs, and methods of producing such molecules. Also disclosed herein are methods of producing libraries of comPACT polynucleotides and polypeptides, and their exemplary use in capturing cancer neoepitope-reactive T cells.

Abstract: The present invention relates to a recombinant microbial system for generation of neo-glycocins, a substrate and to co-evolve its glycosyltransferase enzyme. The recombinant microbial system comprises a gene cassette A encoding for microbial O- and S-glycosyltransferase and its suitable acceptor substrate in conjugation with a cleavable dual affinity tag under the control of two independent inducible promoters. The gene cassette is expressed in a microbial host such as E. coli for the co-expression of glycosyltransferase and its suitable acceptor substrate. The invention further discloses method for production and bioactivity guided screening of O- and or S-neo-glycocins using the recombinant microbial system. The system provides optimized construct design, and methods for high yield production of glycocins and neo-glycocins for downstream applications.

Abstract: The present disclosure relates to T cells capable of co-expressing T cell receptors (“TCR”) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

Abstract: The present disclosure provides a novel technique relating to immunological tolerance. More specifically, the present inventor found for the first time that, in a technique for inducing immunological tolerance by administering an organ transplantation patient (a recipient) a cell preparation containing cells in which anergy is induced by an inhibitor inhibiting the interaction between CD80/CD86 and CD28, the immunological tolerance continues even after the disappearance of the cells derived from the cell preparation from the recipient (infectious immunological tolerance). Further, the present inventor proved that such a cell preparation can elicit immunological tolerance against immunological rejection caused by allergy, iPS cells, etc. or cells, tissues or organs derived therefrom.

Abstract: The disclosure provides polynucleotides containing regions of the Myosin 15 (Myo15) promoter, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss or vestibular dysfunction.

Abstract: Described herein are modified oncolytic viruses that can contain modifications in the viral genome and exogenous nucleic acids coding for proteins. The modified oncolytic virus can be utilized as a platform vector for systemic delivery. Further described herein are oncolytic viruses having an exogenous nucleic acid that codes for a protein or a functional variant thereof that enhances degradation of an extracellular matrix (ECM) associated with a tumor, wherein the protein is a membrane associated protein.

Abstract: The present invention is based, in part, on the identification of an IRE1?-XBP1-cMyc axis in NK cell immunity. The present invention provides compositions and methods for treating conditions that would benefit from modulating (e.g., upregulating or downregulating) an immune response using an agent that modulates the IRE1?-XBP1 pathway, or a composition comprising modified NK cells.

Abstract: Disclosed herein are therapeutic applications of CRISPR/Cpf1-based genome editing.

Abstract: Provided herein are recombinant antigen receptors, for example chimeric antigen receptors (CARs), that comprise modified cytoplasmic domains that provide improved signalling and thereby provide improved performance and safety. Also provided are polynucleotides encoding the recombinant antigen receptors, vectors comprising the polynucleotides, and engineered immune cells comprising the vectors and/or polynucleotides. The invention further provides methods for engineering immune cells to express the recombinant antigen receptors. Improved recombinant antigen receptor signalling is also provided by co-expressing a first recombinant antigen receptor and a second recombinant antigen receptor or co-expressing a recombinant antigen receptor and a protein involved in transducing the signal from the activated recombinant antigen receptor.

Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

Abstract: In some aspects, the disclosure relates to compositions and methods for modulating (e.g., increasing and/or decreasing) bone mass in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that promote (e.g., increase) or inhibit (e.g., decrease) activity, differentiation, or function of certain types of bone cells, for example osteoblasts, osteoclasts, osteocytes, etc. In some embodiments, the isolated nucleic acids and vectors described by the disclosure are useful for treating disorders and conditions associated with increased bone mass (e.g., osteopetrosis) or decreased bone mass (e.g., osteoporosis).

Abstract: Provided herein are compositions that include nucleic acid fragments produced from double-stranded template nucleic acids, such as cell free DNA. The compositions can be used as positive or negative controls for quality of library preparation methods, calibration of an instrument such as a sequencing instrument, and/or a validation for a nucleic acid sequencing test. Also provided are methods for making the nucleic acid fragments.

Abstract: Compositions and methods for producing modified AAV Cap genes and combinatorial libraries of chimeric AAV vectors and virions in an AAV serotype 3 background. Selecting for modified AAV3 virions displaying cell- or tissue-specific tropisms differing from WT AAV3. Using the synthetic combinatorial AAV3 capsid libraries for introducing into a selected target host cells one or more nucleic acid molecules useful in diagnostic and/or therapeutic gene-therapy regimens.

Abstract: The present disclosure provides methods for re-programming effector T cells to a central memory phenotype comprising culturing the effector T cells with a histone deacetylase inhibitor (HDACi) and IL-21. Further provided are methods of treating cancer comprising administering the central memory T cells.