Abstract: Activity-inducible fusion proteins whose activity is post-translationally regulated utilizing a hsp90 binding domain and a drug molecule are described. In the absence of the drug molecule, the activity-inducible fusion proteins are inactivated but can be activated by a relevant physiological parameter in the presence of the drug molecule. Examples of the activity-inducible fusion proteins include chimeric antigen receptors (CAR) wherein the relevant physiological parameter is antigen binding.

Abstract: The present disclosure provides improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

Abstract: Aspects of the invention described herein relate to methods of making and using inducible promoters for transgene expression. The inducible promoters are derived from the NFAT-RE inducible system and are used to improve or enhance T cell survival and proliferation.

Abstract: In Hybrid and truncated immune cell proteins are described. Hybrid proteins are stimulatory and include an extracellular domain of one stimulatory immune cell protein, an intracellular domain of a different stimulatory immune cell protein, and a transmembrane domain linking the extracellular domain to the intracellular domain. Truncated proteins include an immune cell receptor ligand and a transmembrane domain but lack a functional intracellular domain. The hybrid and truncated proteins can be used to modulate and/or diversify immune cell activation in the fight against cancers and infectious diseases, among other uses.

Abstract: Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

Abstract: The present disclosure relates to biomarker profiles and their use to predict a subject's response to an immunomodulatory treatment. Biomarkers in these profiles include cytokines and other proteins associated with the interleukin 1 family and the type 1 interferon family. Particular biomarkers include interleukin (IL)-2, soluble IL-2 receptor alpha (sIL-2RA), IL-5, IL-6, IL-9, IL-10, IL-18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), IL-22, C-type lectin-like receptor (CD161), CD56, interferon gamma (IFN?), granulocyte macrophage colony stimulating factor (GM-CSF), serum amyloid A (SAA), and C-reactive protein (CRP). Particular biomarkers also include populations of cells including CD161+ cells and CD56+dim cells. The biomarker profiles can be used to predict a subject's responsiveness to an immunomodulatory treatment (e.g.

Abstract: The disclosure provides immunogenic peptides comprising at least a portion of a Plasmodium HAP2 paralog (“HAP2p”) protein, immunogenic compositions comprising or encoding the immunogenic peptides, antibodies binding the immunogenic peptides, and methods of preventing Plasmodium transmission incorporating the peptides, compositions, and/or antibodies. In some embodiments, the immunogenic peptide has a sequence comprising a sequence with at least 80% identity to a sequence of at least 10 continuous amino acids of SEQ ID NO:2, a Plasmodium HAP2 paralog (“HAP2p”) protein.

Abstract: The current disclosure provides chimeric antigen receptors (CARs) that bind a natural killer (NK) cell surface marker, resulting in destruction of the bound NK cell. The NK cell surface markers include an activating NK cell receptor, and an inhibitory NK cell receptor. Cells that are genetically modified to express these CARs and uses of the CAR modified cells are also described.

Abstract: Single-domain antibodies that bind the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) spike protein are disclosed. The single-domain antibodies include binding domains that bind epitopes of the Spike ectodomain inside and outside the receptor binding domain. The single-domain antibodies can be used for multiple purposes including in the research, diagnosis, and prophylactic or therapeutic treatment of COVID-19.

Abstract: The use of inhibitors upstream of mTOR in the CSF1 pathway of neuroinflammation, inhibitors of chemokine receptor CXCR3, functional derivatives thereof, and/or immunosuppressant drugs to reduce neuroinflammation are disclosed. The inhibitors and/or immunosuppressant drugs can treat genetic or environmental encephalopathies and/or reduce microglial activation. Treated encephalopathies include Leigh Syndrome and Wernicke encephalopathy.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: Systems, apparatuses, and methods enable rapid, repeatable, and accurate dissection of arthropods. Arthropod dissection apparatuses includes a shear dissection mechanism having a primary shear body and a secondary shear body. The primary shear body includes at least an inlet channel, a first outlet channel, and a second outlet channel formed therein. The secondary shear body is disposed in an aperture of the primary shear body and has a dissection chamber formed therein. The secondary shear body is movable between a first position and a second position relative to the primary shear body, which causes a shearing action at a shearing interface between the secondary shear body and the primary shear body.

Abstract: The current disclosure provides antibodies that bind to peptides associated with the primary immunodeficiency disorders (PIDD) Wiskott-Aldrich Syndrome (WAS) and X-linked agammaglobulinemia (XLA). The antibodies can be used in peptide immunoaffinity enrichment coupled to selected reaction monitoring mass spectrometry (immuno-SRM) assays for clinical diagnosis and newborn screening of WAS and XLA, among other uses.

Abstract: Described herein are aptamers that bind to the transferrin receptor (e.g., CD71) and can be used, in part, for depleting transferrin receptor-expressing cells from a population of therapeutic cells. These aptamer compositions can be used in methods for isolating and/or enriching cells expressing CD71 or depleting cell populations of cells expressing CD71, including for example, tumor cells. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Abstract: Provided herein are compositions comprising aptamers that specifically bind monocytes and/or macrophage and methods for their use. These aptamer compositions can be used in methods for isolating and/or enriching monocytes and/or macrophages or depleting cell populations of monocytes and/or macrophages. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a human Wiskott-Aldrich syndrome gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of WAS, including but not limited to, an immune system disorder, thrombocytopenia, eczema, X-linked thrombocytopenia (XLT), or X-linked neutropenia (XLN).

Abstract: The present invention relates to the discovery that etanercept reduces the rate of resistance to intravenous gamma globulin (IVIG) in subjects with acute Kawasaki disease (KD). In certain embodiments, the co-administration of etanercept and IVIG more effectively treats acute KD in subjects older than 12 months than IVIG alone. In other embodiments, the co-administration of etanercept and IVIG ameliorates coronary artery dilation in high risk subjects.

Abstract: A kit for resuscitating a subject, particularly a neonatal patient, is described. In an embodiment, the kit includes a syringe having a tip defining a male Luer taper fitting, and an adaptor defining a first end portion shaped to couple with the male Luer taper fitting and a second end portion shaped to cooperatively couple with an opening of an endotracheal tube.

Abstract: Provided herein are several monoclonal antibodies that activate the adhesion activity of human and mouse E-cadherin, including the amino acid sequences for the CDRs that define the binding domains of each monoclonal antibody. Also described are methods of making these antibodies, as well as biologically functional fragments and derivatives thereof; and methods of using them in the treatment, prevention, and/or amelioration of disease and conditions characterized by disruption of normal cell adhesion and/or cell junctions. Specifically contemplated are methods and compositions for the treatment of cancer metastasis as well as inflammatory conditions (such as inflammatory bowel disease and airway inflammation).

Abstract: The disclosure provides a panel of biomarkers that individually or in combination can indicate the presence of sepsis as distinguishable from other non-infection related inflammatory conditions. The disclosed biomarkers and related reagents and kits provide strategies for detecting, treating, and monitoring sepsis in subjects. In aspect, the disclosure provides a method for detecting sepsis, comprising contacting a biological sample obtained from the subject with an affinity reagent that specifically binds to one or more of the disclosed novel biomarkers, and detecting differential expression of the one or more biomarkers by detecting binding of the affinity reagent to the biomarker. The method can incorporate use of additional known biomarkers. The method can further comprise treating a subject determined to have sepsis. In some embodiments, the subject is a human subject less than 20 years old.