The present invention relates to a compound decreasing the concentration of 2-hydroxy-glutarate (2HG) in a subject for use in treating, preventing, and/or preventing progression of cardiac remodeling, in particular cardiomyopathy and/or heart failure and to viral particles, compositions, uses and methods related thereto.

The invention relates to a method for providing a drug delivery system, in particular for crossing the blood brain barrier (BBB), comprising a virus-like particle (VLP) derived from John Cunningham virus (JCV), a drug delivery system and novel VLP obtainable by said method. The method comprises steps of disassembly of VLP into pentamers and reassembly into VLP.

Disclosed is an antisense nucleic acid that suppresses NEK6 gene expression.

Disclosed herein is a method for producing an exosome containing therapeutic agent, including: separating tumor cells from a biomaterial sample of a subject; treating the separated tumor cells in a culture media at 37° C. and at 5% CO2 for 24-72 h; separating an exosome composition from the culture media; and dissolving the separated exosome composition in a phosphate buffer to obtain the exosome containing therapeutic agent; characterized in that the culture media comprises either (i) a 1:1 mixture of DMEM/F12 (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12) and HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 2 mmol/mL or 3.65 mg/10 mL of L-glutamine, 100 units/mL of penicillin, 100 μg/mL of streptomycin, and 10 wt % of fetal bovine serum; or (ii) 79 wt % of RPMI, 20 wt % of fetal bovine serum and 1 wt % of streptomycin.

Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

The present disclosure relates to therapeutic exosomes enriched in proteins that are present in the luminal surface of exosomes. The present disclosure provides methods of manufacturing exosomes enriched in proteins that are present in the luminal surface of exosomes, method of associating a therapeutic peptide or protein to the luminal surface of exosomes, and method of use, e.g., methods of therapeutic or diagnostic use. The methods of manufacture involve generating of luminal-surface-engineered exosomes that include one or more of the EV, e.g., exosome proteins at concentrations higher that those observed in wild type exosomes, a modification or a fragment of the EV, e.g., exosome protein, or a fusion protein of the EV, e.g., exosome protein, and a payload, e.g., biologically active molecule such as a therapeutic protein.

Provided herein are compositions comprising EV, e.g., exosome, encapsulated STING agonists and methods of producing the compositions described. Also provided herein are methods of modulating an immune response via administration of a therapeutic amount of EV, e.g., exosomes encapsulating STING agonists. The immune response may be an IENβ response or activation of myeloid dendritic cells (mDCs). Also provided herein are methods of modulating an immune response that does not induce systemic inflammation via administration of exosomes encapsulating STING agonists.

Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

The invention includes systems, methods, and compositions for designing secreted fusogenic ectosome vesicles, or gectosomes, that selectively encapsulate specific target proteins, nucleic acids and/or other small molecules in a predetermined manner. These engineered gectosomes can be used to deliver desired cargos to receipt cells in vitro, ex vivo, or in vivo and may further reprogram target cellular phenotypes in a dose-dependent manner, as well as perform genome editing functions, among others.

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.