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 invention relates to compositions comprising nanoparticles associated with a plurality of tolerogenic antigens (e.g., between 1-30 tolerogenic 5 antigens per nanoparticle) in such a manner that facilitates strong immune tolerance upon administration to a subject (e.g., a human subject suffering from or at risk of suffering from an autoimmune disorder e.g., MS or celiac disease). The present invention further relates to methods for utilizing such nanoparticles to treat autoimmune disorders (e.g., MS or celiac disease).

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 compounds of Formula (I), as well as compositions comprising a compound of Formula (I) and uses thereof.

##STR00001##

The present invention relates to nanoparticles complexed with therapeutic agents configured for treating cardiovascular related disorders, and methods of synthesizing the same. In particular, the present invention is directed to compositions comprising synthetic HDL (sHDL) nanoparticles carrying therapeutic agents configured for treating cardiovascular related disorders, methods for synthesizing such sHDL nanoparticles, as well as systems and methods utilizing such sHDL nanoparticles (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutic agents, imaging agents, and/or targeting agents (e.g., in cardiovascular disease diagnosis and/or therapy, etc.))).

Provided herein are compositions and methods for diagnosis and treatment of early-stage atherosclerotic plaques and reduction of plaques in arteries. In particular, provided herein are high-density-lipoprotein-functionalized magnetic nanostructures (HDL-MNS) capable of (i) precise anatomic detection of atherosclerotic lesions, (ii) removal of excess cholesterol from macrophage cells in atherosclerotic plaque, and/or (iii) delivery of therapeutic agents to plaque locations, and methods of diagnosis and treatment of atherosclerosis.

The invention in aspects relates to methods of treating sepsis using HDL-NP. The methods include the use of nanoparticles having a core and a lipid based shell with optimal lipids therein.

The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Disclosed herein are agents that target cholesterol metabolism (e.g., synthetic nanostructures), pharmaceutical compositions, kits, or methods for treating and/or preventing viral infections. In some embodiments, the agents that target cholesterol metabolism and/or pharmaceutical compositions are delivered to the subject's respiratory system. In some embodiments, the viral infection is caused by a respiratory vims. In some embodiments, the virus is adenovirus (ADV); influenza virus, human bocavims (HBoV); human coronavirus (HCoV); human metapneumo vims (HMPV); human parainfluenza virus (HPIV); human respiratory syncytial vims (HRSV); human rhino vims (HRV); severe acute respiratory syndrome coronavirus (SARS-CoV); and Middle East Respiratory Syndrome coronavirus (MERS-CoV). In some embodiments, the virus is SARS-CoV-2.

A lipid membrane structure encapsulating an siRNA inside thereof and containing a lipid compound of the formula (I) as a lipid component (R.sup.1 and R.sup.2 represent CH.sub.3—(CH.sub.2).sub.n—CH═CH—CH.sub.2—CH═CH—(CH.sub.2).sub.m—, n represents an integer of 3 to 5, m represents an integer of 6 to 10, p represents an integer of 2 to 7, and R.sup.3 and R.sup.4 represent a C.sub.1-4 alkyl group or a C.sub.2-4 alkenyl group.