Abstract: Among the various aspects of the present disclosure is the provision of methods of detecting and treating immunotherapy-resistant B cell malignancies. Methods of detection include detecting a glycosylation state of CD19 or detecting expression or activity of SPPL3 in malignant B cells, comparing to a reference state or value, and determining that the B cell malignancy is resistant to immunotherapy if the glycosylation state of CD19 or expression or activity of SPPL3 is substantially increased or decreased relative to corresponding reference levels. Also provided are therapeutic agents capable of modulating CD19 glycosylation or SPPL3 expression or activity for treatment of B cell malignancies in combination with CD19-targeted immunotherapies.

Abstract: Compositions and methods for effecting base editing to correct mutations in the phenylalanine hydroxylase gene, thereby curing phenylketonuria, are disclosed.

Abstract: A system and method for generating a decision tree having a plurality of nodes, arranged hierarchically as parent nodes and child nodes, comprising: generating a node including: receiving i) training data including data instances, each data instance having a plurality of attributes and a corresponding label, ii) instance weightings, iii) a valid domain for each attribute generated, and iv) an accumulated weighted sum of predictions for a branch of the decision tree; and associating one of a plurality of binary prediction of an attribute with each node including selecting the one of the plurality of binary predictions having a least amount of error; in accordance with a determination that the node includes child nodes, repeat the generating the node step for the child nodes; and in accordance with a determination that the node is a terminal node, associating the terminal node with an outcome classifier; and displaying the decision tree including the plurality of nodes arranged hierarchically.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The present invention includes compositions and methods for a modified immune cell or precursor cell thereof comprising an inducible expression system. Also provided are gene edited modified immune cells suitable for T cell therapy. Methods of treatment using modified immune cells of the present invention are also provided.

Abstract: The present invention relates to compositions and methods for inducing an adaptive immune response against Hepatitis C virus (HCV) in a subject. In some embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof. For example, in some embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof.

Abstract: Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5? inverted terminal repeat (ITR), an expression cassette comprising an open reading frame (ORF) for a mature human Lamin A (hLaminA) under control of a regulatory sequence which direct expression of mature hLaminA in a target cell, and an AAV 3? ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treatment of idiopathic dilated cardiomyopathy (DCM) or a disease associated with a mutation in a Lamin A (LMNA) gene.

Abstract: Formulations and methods for reducing blood glucose and/or increasing insulin signaling in a subject have been developed. The formulations include SBI-477 and compounds based on SBI-477 i.e., SBI-477 analogs (collectively, SBI-477 compounds) and/or Mondo family inhibitors, in an effective amount to inhibit intracellular lipid accumulation and/or increase cellular glucose uptake when compared to levels in a control subject not administered the composition. Also disclosed are methods of reducing intracellular lipid accumulation and/or increase glucose uptake in a subject in need thereof. The method includes administering to the subject an effective amount of SBI-477 compounds and/or Mondo family inhibitor to reducing intracellular lipid accumulation and/or increase glucose uptake in the subject.

Abstract: A computerized method of providing automatic anatomy recognition (AAR) includes gathering image data from patient image sets, formulating precise definitions of each body region and organ and delineating them following the definitions, building hierarchical fuzzy anatomy models of organs for each body region, recognizing and locating organs in given images by employing the hierarchical models, and delineating the organs following the hierarchy. The method may be applied, for example, to body regions including the thorax, abdomen and neck regions to identify organs.

Abstract: Provided are nanoporous materials (including nanoporous metals) and related methods of fabricating the disclosed materials. The disclosed materials are useful in supporting chemical reactions, including the on-board production of hydrogen from water by way of contacting the water to the disclosed materials.

Abstract: Compositions and methods for treating type II diabetes in a subject. A viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding a propeptide and the active portion of GLP-1, wherein, when expressed, the N-terminal amino acid of GLP-1 immediately follows the C-terminal amino acid of the propeptide. In desired embodiments, the subject is a cat or dog.

Abstract: Provided are nanopore devices that include a hafnium oxide coating on the pores of the devices. Such devices exhibit improved stability, especially when in a salt solution environment. Also provided are related methods.

Abstract: Provided herein are compositions and methods for preventing or reducing CARPA in a subject in need thereof. In one aspect, the composition comprises a therapeutic molecule, diagnostic molecule, molecular complex, or nanoparticle having a complement inhibitory protein attached thereto.

Abstract: Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5? inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, optionally comprising stabilizing amino acid changes, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3? ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

Abstract: The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.

Abstract: This invention describes methods for treating wound healing pathologies, inhibiting or reversing fibrotic skin disorders, including but not limited to keloids, atrophic and hypertrophic scars, and reversing skin aging via generating new dermal adipocytes (DAs). Methods described herein comprise (a) grafting of human hair follicles or (b) direct delivery of conditioned media from in vitro cultured hair follicles, or (c) delivery of purified individual factors secreted by hair follicles, or (d) delivery of small molecule agonists that mimic hair derived signaling activities, or (e) delivery of small molecule antagonists that inhibit anti-adipogenic programs, or (f) delivery of small molecule agonists of pro-adipogenic programs to convert endogenous wound or scar skin fibroblasts into new DAs.

Abstract: The invention includes compositions comprising a chimeric antigen receptor (CAR) specific for an GD T Cell receptor (anti-GD TCR CAR), vectors comprising the same, compositions comprising anti-GD TCR CAR vectors packaged in viral particles, and recombinant T cells or other effector cells comprising the anti-GD TCR CAR of the invention. The invention also includes methods of making a genetically modified T cell expressing an anti-GD TCR CAR wherein the expressed CAR comprises an extracellular domain that binds to GD T cells or to cells expressing a GD TCR.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.

Abstract: The invention provides compositions and methods for cancer immunotherapy. Specifically, the invention provides an antigen-presenting cell, for example, a dendritic cell that comprises a tumor mitochondrial molecule or a tumor mitochondrial molecule derived from tumor mitochondrial protein lysate or a specific mitochondria derived protein of mitochondrial protein lysate as antigen source.

Abstract: The invention relates to the use of precursor peptides and B1 proteins from lasso peptide biosynthesis systems for affinity purification, proximity-based sortase-mediated protein purification and ligation, and detection of fusion proteins. For proximity-based sortase-mediated protein purification and ligation, the invention relates to techniques that link protein purification with conjugation to other agents, including therapeutic agents, imaging agents, or linkers.