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.

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.

Provided are modified isolated ADAM10 modulating peptides and methods of using the same to modulate ADAM10 biological activities, inhibit ADAM10 biological activities associated with diseases, disorders, or conditions in subjects, including but not limited to decreasing inflammation and inhibiting undesirablecell proliferation. In some embodiments, the modified isolated ADAM10 modulating peptides are based on SEQ ID NO: 3 or SEQ ID NO: 4, and in some embodiments include modifications at or near the N-terminal and/or the C-terminal ends of the disclosed peptides as well as substitutions, insertions, and deletions at one or more amino acid positions of the ADAM10 prodomain peptides disclosed herein.

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.

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.

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.

The present disclosure relates to a method for detecting a brain injury in a subject by comparing the amount of ADAM10 protein in a blood sample from the subject to a reference standard or to the amount of ADAM10 in a blood sample from a control. An increase in the amount of ADAM10 in the subject blood sample relative to the reference standard or control is indicative of the subject having sustained a brain injury, in particular a traumatic brain injury (TBI). The present disclosure also provides novel antibody and antibody fragments that bind to ADAM10 at different positions.

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.

Provided herein are methods and compositions related to TREM2 mutants resistant to sheddase cleavage, e.g., human TREM2 mutants resistant to sheddase cleavage, and nucleic acids encoding such TREM2 mutants resistant to sheddase cleavage.

Provided are modified isolated ADAM10 modulating peptides and methods of using the same to modulate ADAM10 biological activities, inhibit ADAM10 biological activities associated with diseases, disorders, or conditions in subjects, including but not limited to decreasing inflammation and inhibiting undesirable cell proliferation. In some embodiments, the modified isolated ADAM10 modulating peptides are based on SEQ ID NO: 3 or SEQ ID NO: 4, and in some embodiments include modifications at or near the N-terminal and/or the C-terminal ends of the disclosed peptides as well as substitutions, insertions, and deletions at one or more amino acid positions of the ADAM10 prodomain peptides disclosed herein.