Abstract: A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell, including: contacting a permeabilized cell or nucleus with a specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the specific binding agent is linked to a nuclease that is inactive or an activatable transposome; activating the nuclease or transposase, thereby excising the sequence of chromatin DNA bound to the chromatin-associated factor of interest; isolating the excised DNA; and determining the sequence of the excised DNA, thereby detecting binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in the cell.

Abstract: IgM-multimerized single-domain antibodies that bind receptor tyrosine kinase (ROR1) are described. The IgM-multimerized single-domain antibodies can be used for multiple purposes including in research, imaging, diagnosis, and treatment of ROR1-related conditions and can be conjugated to form multi-domain binding molecules or antibody conjugates.

Abstract: Circular handed alpha-helical repeat proteins are described. The repeat proteins have a number of uses as scaffolds for geometrically precise, arrayed presentation of cell-signaling or immune-related protein and peptide epitopes, as well as numerous other therapeutic, diagnostic, and nanotechnological uses.

Abstract: The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

Abstract: The disclosure provides artificial nucleic acid introns configured for selective splicing in cells with aberrant RNA splicing activity, e.g., neoplastic cells. The artificial intron can comprise a 5? splice site, a canonical 3? splice site, at least one cryptic 3? splice site, a pyrimidine-rich domain, and at least one branchpoint. Also provided are constructs integrating the artificial introns with exons in a configuration that, when the artificial intron is spliced out by the aberrant RNA splicing factors, encode a functional protein. Also disclosed are methods that employ the disclosed platform of selective expression, including, targeted gene therapy methods (e.g., in cancers), diagnostics and imaging, and drug screening.

Abstract: Compositions and methods that rapidly and selectively modify hematopoietic stem cells (or cells derived therefrom) to achieve therapeutic objectives by providing for transient expression of nucleic acids are described. The transient expression leads to permanent therapeutic changes in the modified cells, referred to herein as “hit and run” effects.

Abstract: In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.

Abstract: Disclosed herein are to markers, methods and systems for identifying cell populations, diagnosing, monitoring and treating cancer, including biomarkers predictive of response to immunotherapy treatment in Merkel cell carcinoma.

Abstract: A method of treating prostate cancer based on determining genome-wide methylation profile at a plurality of transcription factor binding sites in the total DNA obtained from cell-free biological samples from a subject suffering from prostate cancer are provided herein. Also described are methods for determining suitable treatment regimens for prostate cancer and methods for treating prostate cancer patients, based around selection of the patients according to the methods of the disclosure. The disclosure also relates to computer-implemented methods for identifying, diagnosing, staging, or otherwise characterizing cancers, in particular advanced prostate cancer. The methods of the present disclosure relate, inter alia, to isolating and analyzing the human DNA component from cell-free samples.

Abstract: The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with ?-secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with ?-secretase inhibitor can be used in, for example, adoptive immunotherapy.

Abstract: SARS-CoV-2 vaccines are described herein. The SARS-CoV-2 vaccine antigens can be presented on a circular tandem repeat protein (cTRP) scaffold as trimers or tetramers. The vaccines can be used to treat and/or reduce the risk of SARS-CoV-2 infection and to treat and/or reduce the risk of side effects associated with SARS-CoV-2 infection, such as SARS-CoV-2-related symptoms, syndromes, and complications.

Abstract: The disclosure provides compositions and related methods for detecting, inhibiting, reducing or killing tumor-infiltrating regulatory T cells (Tregs) characterized by expression of inducible T cell costimulator (ICOS) and Interleukin-1 receptor type 1 (IL-1R1). The reagents can include a bi-specific affinity reagent with a first domain that specifically binds ICOS and a second domain that specifically binds IL-1R1 or, separately, a first affinity reagent that specifically binds ICOS and a second affinity reagent that specifically binds IL-1R1. In some embodiments, the reagent can comprise engineered immune cells expressing a first chimeric antigen receptor (CAR) specific for ICOS and a second CAR specific for IL-1R1, wherein the cell requires binding by the first CAR and second CAR to activate, such as a logic-gated CAR T cell.

Abstract: The present disclosure provides compositions and uses thereof for treating a disease or disorder associated with CD20 expression. Treatments of this disclosure include use of a host cell expressing a fusion protein, such as an anti-CD20 CAR, optionally in combination with a CD20-specific binding molecule, a chemotherapeutic, an inhibitor of an immunosuppression component, or combinations thereof.

Abstract: Stem cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to detect, enrich, isolate, activate, track, deplete, or eliminate modified cells. The cells can be administered before or following differentiation into a more committed cell type.

Abstract: Methods to create barcoded influenza viruses without disrupting the function of the viral proteins and the proper packaging of the viral genome segments are described. The barcoded influenza viruses can be used within deep mutational scanning libraries to map influenza resistance mutations to therapeutic treatments. The libraries can also be used to predict influenza strains that may become resistant to therapeutic treatments and/or more easily evolve to infect new species. The libraries include features that allow efficient collection and assessment of informative data, obviating bottlenecks of previous approaches.

Abstract: Nanoparticle systems that genetically modify monocytes/macrophages in vivo to (1) recruit additional immune cells to a treatment site; (2) remain activated at the treatment site providing an on-going stimulatory signal to other immune cells; and (3) secrete bispecific immune-cell engaging antibodies that bind antigens on cells of interest at the treatment site and also bind and activate the recruited immune cells to destroy the bound cell. The systems can also inhibit the activity of transforming growth factor beta (TGF?).

Abstract: The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.

Abstract: The current disclosure provides recombinant adenoviral vectors and adenoviral genomes that can accommodate or that contain a large transposon payload, for instance a transposon payload of up to 40 kb. The adenoviral vectors and genomes can deliver the large transposon payload into a target genome, for instance for gene therapy.

Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.

Abstract: The present disclosure is based on the discovery that a clinical grade compound of Formula (I) potently blocks TGF-? activity and significantly reverse the activated phenotypes of myofibroblast in vitro. The compound of Formula (I) can be used in the treatment of fibrotic conditions in general, such as non-alcoholic steatohepatitis (NASH), cirrhosis, HBV infection, any liver disease, pulmonary fibrosis, interstitial lung disease, idiopathic pulmonary fibrosis (IPF), renal fibrosis, cardiac fibrosis, or any combination thereof.