Disclosed herein are extracellular vesicles such as exosomes that selectively target cells such as skeletal muscle cells. Such vesicles include skeletal muscle targeting moieties and can be used to selectively deliver a payload to skeletal muscle cells or tissue.

The present invention relates to dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) comprising a polymer core comprising a heme oxygenase 1 inhibitor and a lipid membrane (shell) comprising a targeting moiety, a kit for preparing the dual-targeting lipid-polymer hybrid nanoparticles, a pharmaceutical composition comprising the dual-targeting lipid-polymer hybrid nanoparticles as an active ingredient, and a method of preventing or treating cancer comprising administering the pharmaceutical composition to a subject in need thereof. Accordingly, the present invention can provide the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) comprising a polymer core comprising a heme oxygenase 1 inhibitor and a lipid membrane (shell) comprising a targeting moiety, the kit for preparing the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs), the pharmaceutical composition comprising the dual-targeting lipid-polymer hybrid nanoparticles (T-hNPs) as an active ingredient, and the method of preventing or treating cancer comprising administering the pharmaceutical composition to a subject in need thereof.

The present invention provides compositions comprising nucleic acid molecules, such as mRNA molecules, encapsulated within lipid particles. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a 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 methods of using exosomes that function like minicells to deliver therapeutic agents to diseased or disordered cells. In particular, the exosomes can be targeted to particular areas of the body using growth factor gradients. These gradients also serve to trigger expression of proteins inside the exosomes, from transfected nucleic acids, at the desired target.

The instant disclosure relates to nanoparticle compositions that may be used for the targeting of certain cells or tissues. The nanoparticles may take a variety of different forms, including non-viral, viral, and lipid nanoparticles, and may utilize a TNF receptor superfamily member 12A (“TWEAKR”) binding region of the TWEAK protein to target a nanoparticle to tissues expressing TWEAKR. The compositions may further comprise a suicide gene optionally under the control of a tissue specific promoter. In further aspects, methods of treating an individual using the disclosed nanoparticle compositions are described.

In various implementations, berberine metabolites, such as dihydroberberine and/or tetrahydroberberine, may be administered to manage blood glucose levels, increase ketone levels (e.g., blood concentration of ketones), and/or for therapeutic purposes in humans. The administration of a pharmaceutically effective amount of berberine metabolites, such as dihydroberberine, may reduce fasting blood glucose levels, improve glucose tolerance, and/or improve blood ketone response. In some implementations, berberine metabolites may be administered with one or more other compounds.

Isolated peptides targeting cardiovascular disease are described herein or one or more conservative amino acid substitutions, deletions or additions of such peptides and methods of use thereof for delivering payloads to specific cell types or tissues.

The present invention provides, among other things, improved methods and pharmaceutical compositions for treating cystic fibrosis based on codon optimized mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.

Formulated and/or co-formulated liposomes comprising TLR prodrugs and/or TLR Lipid Moieties and methods of making the liposomes are disclosed herein. The TLR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit Toll-Like Receptor (e.g., TLR1/2, TLR4, and/or TLR7). The TLR prodrugs can be formulated and/or co-formulated into a liposome to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.