Abstract: Provided herein are engineered cells and methods for engineering cells to deliver a therapeutic agent, e.g., a small molecule, peptide or other drug, to a cell or tissue to be treated.

Abstract: The invention relates to a method for producing a lymphocyte progenitor, the method comprising culturing a pluripotent stem cell (PSC)-derived CD34+ cell at an air-liquid interface (ALI). The invention also relates to a method for producing a B-cell progenitor, the method comprising co-culturing a PSC-derived CD34+ cell and a stromal cell in a medium comprising a CD117 activator and a NOTCH1 inhibitor. The invention further relates to a T-cell progenitor and a B-cell progenitor when produced by the methods of the invention and to use of the T-cell progenitor in the manufacture of T cell with defined antigen specificity, optionally a chimeric antigen receptor (CAR) T cell, and use of the B-cell progenitor in the manufacture of an antibody.

Abstract: Provided herein are engineered cells and methods for engineering cells to deliver a therapeutic agent, e.g., a small molecule, peptide or other drug, to a cell or tissue to be treated.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: The invention relates to a vector comprising: a 5? nucleic acid that is homologous to a genomic sequence 5? of a stop codon of a constitutively expressed gene; an exogenous nucleic acid; a 3? nucleic acid that is homologous to a genomic sequence 3? of the stop codon of the constitutively expressed gene; a translation interruption-reinitiation signal operably linked to the 5? nucleic acid and the exogenous nucleic acid, wherein the translation interruption-reinitiation signal is capable of replacing the stop codon of the constitutively expressed gene.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: The present disclosure provides isolated antibodies that bind to acetaminophen-protein adducts that are useful in the detection and diagnosis of acetaminophen-induced toxicity.

Abstract: In vivo gene therapies for immune deficiencies are described. The in vivo gene therapies utilize a foamy viral vector including a PGK promoter with a therapeutic gene. The foamy viral vector can be beneficially administered with cell mobilization into the peripheral blood.

Abstract: A method for determining a likelihood of appendicitis in a subject is disclosed. The method comprises the steps of (a) determining the relative abundance of microorganisms corresponding to one or more operational taxonomic units (OTUs) in a test biological sample obtained from the subject; (b) comparing the relative abundance of the microorganisms in each of the one or more OTUs to a corresponding reference value assigned to each of the one or more OTUs, and (c) determining a likelihood of appendicitis in the subject based on the result in step (b), wherein a significant increase in relative abundance of the microorganisms in the one or more OTUs indicates a high risk of appendicitis in the subject. Also disclosed is a kit for determining a likelihood of appendicitis in a subject.

Abstract: The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP 2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.

Abstract: This invention relates to cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) protein compositions and their use in the mitigation of autoimmune adverse events associated with cancer immunotherapy. Specifically, the disclosure provides a CTLA-4 protein comprising a mutant extracellular domain of CTLA-4, wherein the CTLA-4 protein exhibits reduced binding to an anti-CTLA-4 antibody as compared to a wild-type extracellular domain of CTLA-4, wherein the anti-CTLA-4 antibody has anti-cancer immunotherapeutic activity.

Abstract: Provided herein are methods of sorting antigen-specific IgM memory B cells (MBCs), compositions and methods comprising such antigen-specific IgM MBCs, and recombinant antibody or antigen-binding fragments isolated from such antigen-specific IgM MBCs. As demonstrated herein, IgM and IgD MBCs are unique populations of cells with distinct phenotypic, functional and survival properties. Accordingly, the antigen-specific IgM MBCs and antibodies and antigen-binding fragments derived from these cells described herein are useful in therapeutic applications in vaccine strategies and treatment of infectious diseases.

Abstract: The present disclosure teaches the treatment of a blood pathology, such as a blood pathology associated with impaired hemoglobin synthesis including the treatment of ?-thalassemia or a related hemoglobinopathy. An RNA molecule such as a short interfering RNA or a hairpin RNA which targets an mRNA species encoding ?-globin is administered to a subject to reduce the amount of ?-globin produced to non-zero levels and ameliorate the effects of an ?- and ?-globin chain imbalance.

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: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.

Abstract: The present disclosure relates generally to the field of epigenetics and in particular epigenetic profiles associated with a pathological condition. The present specification teaches screening of individuals and populations for epigenetic profiles associated with a pathological condition. The epigenetic profiles can be from an intron, an intron/exon boundary or a splicing region. Epigenetic profiles are disclosed from the following sites in the FMR locus: FREE3, intron 2 of FMR1, the genomic FREE2 region as a whole or specific FREE2 fragments including FREE2 (D) or FREE2 (E). Kits and diagnostic assays are also taught herein as are computer programs to monitor changes in epigenetic patterns and profiles. Further enabled herein is a method for screening for agents which can reduce or mask the adverse effects of epigenetic modification and the use of these agents in therapy and prophylaxis.

Abstract: A method of treating a waste evacuation dysfunction comprising administering transcutaneous electrical stimulation (TES) to at least one lower pelvic and/or sacral region for a specific treatment regimen. Also disclosed is a system for configuring a stimulation device to deliver transcutaneous electrical stimulation (TES) the system comprising: a computing device storing or having access to a plurality of TES settings and comprising a user interface to enable authorized selection of at least one of the TES settings for provision of TES by the stimulation device according to the at least one selected TES setting and the stimulation device communicatively coupled to the computing device to receive and store the selected at least one TES setting the stimulation device being of a size to be readily carried on a body and configured to selectively provide current to external electrode according to the one TES setting.

Abstract: The present invention relates generally to the field of allergies. More particularly, the present invention provides a method for treating an allergy in a subject by inducing tolerance to an allergen associated with the allergy. Medicinal kits useful in protocols to induce tolerance or reduce intolerance in a subject also form part of the present invention.

Abstract: The present disclosure relates generally to the field of viral vaccines. Particularly, the present disclosure provides a modified Vero-adapted human rotavirus strain and a culturing method to produce high titer virus, a rotavirus vaccine, vaccination protocols and diagnostic and prognostic assays.

Abstract: Some embodiments relate to a method of treating a waste evacuation dysfunction, comprising administering transcutaneous electrical stimulation to at least one lumbar or abdominal region for at least one treatment period per day over a treatment term of at least one week.