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.

Abstract: Hybrid reverse transcriptases are provided that comprise a non-retroviral retrotransposon, or a fragment of the non-retroviral retrotransposon having reverse transcriptase activity, joined to a nucleic acid binding protein. Also provided are methods of using the hybrid reverse transcriptases to prepare a cDNA molecule library.

Abstract: A method of treating a subject having cancer is described that includes administering a therapeutically effective amount of a ?-(1,3)-(1,4) glucan to the subject. Methods of immunostimulating in a subject by administering an effective amount of a ?-(1,3)-(1,4) glucan to the subject are also described.

Abstract: The present invention provides methods for using drain fluid obtained from medical procedures to assess diagnostic biomarkers indicative of disease obtained from drain fluid. In some embodiments, the diagnostics biomarkers are cell-free nucleic acids. In some embodiments, the disease is cancer. In some embodiments, a library of cfDNA is prepared and/or sequenced. In some embodiments, the methods comprise extracting nucleic acid from surgical drain fluid; conducting a size selection procedure to isolate cell-free nucleic acid from the surgical drain fluid; and detecting the cell-free nucleic acid.

Abstract: Disclosed are compositions, methods, and kits for performing cell-free RNA transcription and/or cell-free protein synthesis (CFPS). The disclosed compositions, methods, and kits include or utilize components prepared from a species of Clostridia such as cellular extracts from Clostridium autoethanogenum.

Abstract: Immune cell engineered to inhibit the endogenous expression of one or more of Blimp-1 and A20 and/or overexpress one or more of exogenous TCF7 and Bach2. Method of treating cancer, comprising administering the cells described herein. Method of increasing one or more of a peak fold proliferation rate, a killing efficiency, or inducing the cellular characteristics associated with naïve phenotype of an immune cell, comprising introducing an exogenous construct encoding a CAR or a TCR, and inhibiting the endogenous expression of one or more of Blimp-1 and A20, and/or introducing an exogenous construct encoding one or more of TCF7 and Bach2. Method of generating a modified immune cell, comprising introducing an exogenous construct encoding a CAR or a TCR, and inhibiting the endogenous expression of one or more of Blimp-1 and A20, and/or introducing an exogenous construct encoding one or more of TCF7 and Bach2.

Abstract: Compositions and methods for synthesizing an RNA product are provided herein. For example, the present disclosure provides a method of producing an RNA product comprising incubating an in vitro transcription mixture, thereby producing an RNA product that comprises a plurality of single-stranded RNA molecules. In some embodiments, an in vitro transcription mixture comprises a DNA template comprising an RNA polymerase promoter sequence operatively linked to a target sequence; at least one RNA polymerase that recognizes the RNA polymerase promoter sequence; a plurality of ribonucleotides comprising at least two different types of ribonucleotides, each type comprising a different nucleoside; and a transcription buffer comprising an osmolyte.

Abstract: This invention provides methods for detecting RNAs in a biological sample while using only a small amount of sample input, e.g., less than or equal to 1 mL. The methods described herein are able to detect a large percentage of protein-coding genes having the ENSEMBL gene annotation HG38.

Abstract: The present invention relates to a vector for use in the treatment of a polyglutamine repeat spinocerebellar ataxia, which vector comprises cholesterol 24-hydroxylase encoding nucleic acid.

Abstract: Produced the gene therapy DNA vectors based on the gene therapy DNA vector VTvaf17 for the treatment of diseases featuring disruption of mucociliary transport, mucolytic function and development of mucostasis. The gene therapy DNA vector contains the coding region of the SKI, TGFB3, TIMP2 or FMOD therapeutic genes. Methods of producing or use a gene therapy DNA vector based on gene therapy DNA vector VTvaf17 carrying SKI, TGFB3, TIMP2 or FMOD therapeutic genes. The methods of producing strain for production of gene therapy DNA vector for treatment of diseases featuring disruption of mucociliary transport and development of mucostasis. Escherichia coli strain SCS 110-AF/VTvaf17-SKI, SCS 110-AF/VTvaf17-TGFB3, SCS110-AF/VTvaf17-TIMP2 or SCSI 10-AF/VTvaf17-FMOD obtains by the method described above carrying gene therapy DNA vector VTvaf17-SKI, VTvaf17-TGFB3, VTvaf17-TIMP2 or VTvaf17-FMOD.

Abstract: The invention includes a method of evaluating a bovine embryo by fertilizing an egg obtained from a first bovine heterozygote of a recessive lethal haplotype with sperm cells obtained from a second bovine heterozygote of the recessive lethal haplotype; producing the embryo from the fertilized egg, wherein the embryo is homozygous for the lethal haplotype; establishing a cell culture from the embryo; collecting a plurality of cultured cells; and obtaining omics data, comprising one or more features, from the plurality of cultured cells.

Abstract: Methods and Kits for analyzing macromolecules, including peptides, polypeptides, and proteins, employing nucleic acid encoding are disclosed. The sample analysis kits employ nucleic acid encoding and/or nucleic acid recording of a molecular interaction and/or reaction, such as recognition events (e.g., between an antigen and an antibody, between a modified terminal amino acid residue, or between a small molecule or peptide therapeutic and a target, etc.). Assays that do not require the cyclic transfer of information between a coding tag and a recording tag are also disclosed, including single cycle assays.

Abstract: The application provides gene therapies for treating monogenic forms of nephrotic syndrome.

Abstract: Compositions for the in vivo delivery of a gene editing CRISPR/Cas9 complex was developed to eliminate integrated retroviral DNA sequences from latently infected human cells and animal disease models.