Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5′ inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3′ ITR. Also provided herein are methods of treating Batten disease comprising administering to a subject in need thereof the rAAV described herein via more than one route. Also provide herein are pharmaceutical compositions comprising the rAAV described herein and related methods of treating Batten disease.

The present invention relates to engineered extracellular vesicles (EVs) as a novel therapeutic approach to treating urea cycle disorders. More specifically, the invention relates to the use of various protein engineering and nucleic acid engineering strategies for improving loading of urea cycle proteins or nucleic acids encoding urea cycle proteins into EVs and targeting of the resultant EVs to tissues and organs of interest.

An object of the present invention is to develop and provide a method for conveniently introducing a nucleic acid, a peptide, and/or a low-molecular-weight compound into an empty capsid with viral early infection activities kept. The present invention provides a method for producing a drug delivery particle, comprising the steps of: mixing an empty capsid or an empty particle with a drug including a nucleic acid, a peptide, and/or a low-molecular-weight compound in a solution comprising 0.1 to 20% of a surfactant; and keeping the obtained mixed solution at −5 to 50° C. to introduce the drug into the empty capsid or the empty particle.

An isoform of the TGF beta receptor II comprising a sequence of about of 80 amino acids and lacking a transmembrane domain. The isoform comprises the amino acid sequence set forth in SEQ ID No. 12. The isoform may have the amino acid sequence set forth in SEQ ID No. 2 or sequences having at least 85% sequence identity to the sequence set forth in SEQ ID No. 2. A fusion peptide is provided comprising an isoform of the TGF beta II receptor fused to a ligand, wherein a vector comprising the fusion peptide is used to treat cancer and/or hepatic fibrosis. An antibody binding the soluble isoform of the TGF beta II receptor is provided. The antibody binds the amino acid sequence shown in SEQ ID No. 12 and is used in in vitro methods.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

This invention is directed to, inter alia, compositions and methods for restoring normal microRNA (miR) expression in chondrosarcoma cells as well as methods for treating and diagnosing chondrosarcoma in individuals in need thereof.

The present disclosure provides for an engineered exosome or extracellular vesicle, wherein the engineered exosome or extracellular vesicle is substantially devoid of endogenous nucleic acids and can comprise at least one targeting moiety and/or at least one payload or cargo. The payload or cargo can be a diagnostic agent or a therapeutic agent such as exogenous nucleic acids and/or a CRISPR/Cas system for gene editing. The engineered exosomes can be used to treat disease.

Embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector protein is a Type V effector protein. In certain other example embodiments, the Type V effector protein is Cpf1. Embodiments disclosed herein are directed to viral vectors for delivery of CRISPR-Cas effector proteins, including Cpf1. In certain example embodiments, the vectors are designed so as to allow packaging of the CRISPR-Cas effector protein within a single vector. There is also an increased interest in the design of compact promoters for packing and thus expressing larger transgenes for targeted delivery and tissue-specificity. Thus, in another aspect certain embodiments disclosed herein are directed to delivery vectors, constructs, and methods of delivering larger genes for systemic delivery.

Disclosed are compositions comprising chimeric antigen receptors (CARs) and related methods of use in cancer immunotherapy. Compositions include reprogrammed immune cells (e.g., macrophages, neutrophils, dendritic cells, and T cells) that are metabolically fit for tumor microenvironments. The engineered immune cells are reprogrammed to express one or more of recombinant CARs at their cell surfaces and are loaded with glycolysis accelerating metabolites (e.g., F16BP or succinate). Methods of treating a subject with a condition, such as cancer, are also disclosed and include administering an effective amount of a composition comprising an engineered immune cell to a subject in need thereof.

A composition comprising a population of plant-derived extracellular vesicles (EVs) having a diameter ranging from 10 to 500 nm and showing pro-angiogenic, and anti-bacterial activity, for use in therapeutic applications is provided. A method for loading one or more negatively-charged biologically-active molecules into the population of plant-derived extracellular vesicles (EVs) is also provided.