The present invention features methods and compositions for preventing, inhibiting, or reducing the sensation of itch (pruritus) by modulating the gene expression of TMEM184B. Modulating the gene expression of TMEM184B may comprise increasing Tmem184B protein expression, increasing Tmem184B protein activity or both. Furthermore, the methods and compositions described herein may activate the Tmem184B protein or activate a pathway leading to Tmem184B activation. Additionally, the methods and compositions for modulating the gene expression of TMEM184B may be used to help prevent or treat certain diseases or conditions such as dermatitis.

The present invention provides methods and compositions relating to an assay for hERG channel protein sensitivity to small molecule pharmacological agents. In one embodiment, the invention includes an engineered hERG channel protein. In another embodiment, the invention includes a method of identifying small molecule pharmacological agents that interfere with repolarization of cardiac cells.

In some aspects, fusosome compositions and methods are described herein that comprise membrane enclosed preparations, comprising a fusogen. In some embodiments, the fusosome can the target cell, thereby delivering complex biologic agents to the target cell cytoplasm.

In some aspects, fusosome compositions and methods are described herein that comprise membrane enclosed preparations, comprising a fusogen. In some embodiments, the fusosome can the target cell, thereby delivering complex biologic agents to the target cell cytoplasm.

The present invention relates to a method for preparation of monodisperse cell-targeting giant unilamellar vesicles based on symmetrically division of a parent polymer shell-stabilized giant unilamellar vesicle into smaller polymer shell-stabilized giant unilamellar vesicles with a diameter between 1 μm and 10 μm using a microfluidic splitting device. The inventive method allows preparation of differently charged giant unilamellar vesicles as well as bioligand- and PEG-conjugated giant unilamellar vesicles, which are useful for targeted cellular delivery at high efficiency and specificity. A further advantage of the present invention is that the giant unilamellar vesicles can deliver huge cargos such as drug releasing porous microparticles, high amounts of in vivo imaging probes, viruses, or up-and-coming DNA origami robots.

The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements that promote specificity for target cells, e.g., one or more of a fusogen, a positive target cell-specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosome comprises one or more modifications that decrease an immune response against the fusosome.

According to the present invention, there is provided a composition comprising a population of mitochondria with a smaller size and a population of lipid membrane-based vesicles encapsulating mitochondria in a closed space and a method for producing the composition.

According to the present invention, there is provided a composition comprising a population of mitochondria with a smaller size and a population of lipid membrane-based vesicles encapsulating mitochondria in a closed space and a method for producing the composition.

In some embodiments provided herein is a method of treating pain, the method comprising administering into the subject

a pharmaceutical composition comprising multivesicular liposomes encapsulating bupivacaine phosphate, said multivesicular liposomes comprising

bupivacaine or a salt thereof;

phosphoric acid;

a lipid component comprising at least one amphipathic lipid and at least one neutral lipid lacking a hydrophilic head group; and,

optionally, a cholesterol and/or a plant sterol wherein said multivesicular liposomes are made by a process comprising:

a) preparing a first aqueous component comprising phosphoric acid;

b) preparing a lipid component comprising at least one organic solvent, at least one amphipathic lipid, and at least one neutral lipid lacking a hydrophilic head group;

c) mixing said first aqueous component and said lipid component to form a water-in-oil emulsion, wherein at least one component comprises bupivacaine or a salt thereof;

d) mixing said water-in-oil emulsion with a second aqueous component to form solvent spherules; and

e) removing the organic solvent from the solvent spherules to form multivesicular liposomes encapsulating bupivacaine phosphate,

wherein inadvertent administration of the pharmaceutical composition into the vasculature of the subject does not result in cardiac side effects or CNS side effects in the subject.

In some embodiments provided herein is a method of treating pain, the method comprising administering into the subject

a pharmaceutical composition comprising multivesicular liposomes encapsulating bupivacaine phosphate, said multivesicular liposomes comprising

bupivacaine or a salt thereof;

phosphoric acid;

a lipid component comprising at least one amphipathic lipid and at least one neutral lipid lacking a hydrophilic head group; and,

optionally, a cholesterol and/or a plant sterol wherein said multivesicular liposomes are made by a process comprising:

a) preparing a first aqueous component comprising phosphoric acid;

b) preparing a lipid component comprising at least one organic solvent, at least one amphipathic lipid, and at least one neutral lipid lacking a hydrophilic head group;

c) mixing said first aqueous component and said lipid component to form a water-in-oil emulsion, wherein at least one component comprises bupivacaine or a salt thereof;

d) mixing said water-in-oil emulsion with a second aqueous component to form solvent spherules; and

e) removing the organic solvent from the solvent spherules to form multivesicular liposomes encapsulating bupivacaine phosphate,

wherein inadvertent administration of the pharmaceutical composition into the vasculature of the subject does not result in cardiac side effects or CNS side effects in the subject.