Described herein are RPE cells engineered to secrete a FVII protein, as well as compositions, pharmaceutical preparations, and implantable devices comprising the engineered RPE cells, and methods of making and using the same for treating a patient with hemophilia or FVII deficiency.

The present invention provides a generic platform for delivering molecules with low blood-brain barrier (BBB) penetration into the brain. The nano-delivery system is based on a core nanoparticle which is conjugated through a first polymeric linker to a brain-internalizing transporter moiety, and is further conjugated to a second polymeric linker bound to an active agent selected rom a biologically active molecule or a labeling molecule. Further provided is a process for preparation of the nano-delivery system. The present invention further provides pharmaceutical compositions comprising the nano-delivery system and its use in therapeutic and/or diagnostic methods.

Many tumors induce and maintain an immunosuppressive tumor microenvironment (TME) that enables tumor to escape host immune system. The present disclosure identifies that cancer cells secrete exosome/microparticle-free, soluble, phosphorylated Hsp70 (pHsp70 (Heat Shock Protein 70 (Hsp70))), which triggers macrophage (M) M2 polarization. It is a further aspect that lipid nanovesicles (NVs) made of dioleoylphosphatidylglycerol (DOPG) and of DOPG complexed with saposin C (SapC) bind to cancer secreted Hsp70, inhibit M differentiation and polarization, and reduce tumor growth. In addition, administration of DOPG-NVs rendered monocytes insensitive to TLR2 (Toll Like Receptor 2) and TLR6 (Toll Like Receptor 6) ligands, suggesting that administration of DOPG-NVs interferes with TLR function.

Many tumors induce and maintain an immunosuppressive tumor microenvironment (TME) that enables tumor to escape host immune system. The present disclosure identifies that cancer cells secrete exosome/microparticle-free, soluble, phosphorylated Hsp70 (pHsp70 (Heat Shock Protein 70 (Hsp70))), which triggers macrophage (M) M2 polarization. It is a further aspect that lipid nanovesicles (NVs) made of dioleoylphosphatidylglycerol (DOPG) and of DOPG complexed with saposin C (SapC) bind to cancer secreted Hsp70, inhibit M differentiation and polarization, and reduce tumor growth. In addition, administration of DOPG-NVs rendered monocytes insensitive to TLR2 (Toll Like Receptor 2) and TLR6 (Toll Like Receptor 6) ligands, suggesting that administration of DOPG-NVs interferes with TLR function.

Therapeutic methods and compositions for the in utero or postnatal treatment of diseases associated with alternative splicing are provided. Compositions of the disclosure include delivery nanoparticles with an inner region surrounded by a nucleic acid scaffolding that is, in turn, linked to therapeutic agents that promote healthy mRNA splicing phenotypes in fetal cells when the compositions are delivered to a fetus in utero or in a patient after birth. The nanoparticles preferably include targeting complexes or antibodies that promote endosomal uptake into such cells and escape peptides that release the nanoparticles from endosomes into the cytosol within the cells to allow the therapeutic agents to promote preferred splicing

The present disclosure provides a gene editing nanocapsule and a preparation method and use thereof. The gene editing nanocapsule has a core-shell structure, wherein the inner core includes a Cas/sgRNA ribonucleoprotein complex, and the outer shell includes a polymer, the Cas/sgRNA ribonucleoprotein complex has a gene editing function, and the polymer acts as a carrier for the Cas/sgRNA ribonucleoprotein complex and protects it, because the polymer contains tumor microenvironment sensitive molecules, the nanocapsules can be efficiently released in tumor cells. Further, the surface of the outer shell can be modified with a targeting agent, so that the nanocapsule can specifically target tumor cells, which improves the endocytosis efficiency of the nanocapsule. The gene editing nanocapsule has good biocompatibility and biosafety, and is expected to become a safe and efficient gene therapy drug for tumors.

The present disclosure relates to nanoparticles for delivering a drug targeting brain cancer, whose surface is modified with a peptide for targeting brain cancer, a preparation method thereof, and a use thereof, and more particularly, to nanoparticles for delivering a drug targeting brain cancer, including porous silicon nanoparticles encapsulating an anticancer drug and a peptide with an ability to target brain cancer cells bound to the surface of the nanoparticles, a preparation method thereof, and a use thereof. The nanoparticles according to the present disclosure can be used as an effective drug delivery system for treating glioblastoma by allowing a conventional anticancer agent exhibiting low tissue specificity and solubility to be specifically delivered to glioblastoma in which a caveolin receptor is overexpressed through the blood-brain barrier to induce a more efficient glioblastoma therapeutic effect.

Multifunctional nanoparticle for targeted therapeutic drug delivery, comprising (a) an iron oxide core having silica-polyethylene glycol coupled thereto to provide an iron oxide coated core, (b) a cytotoxic agent reversibly associated with the coated core; (c) an immunomodulating agent reversibly associate with the coated core; and (d) a tumor targeting agent associated with the coated core. Methods for using the nanoparticle to treat cancers and methods for making the nanoparticle.

The present invention pertains to inter alia methods for purifying extracellular vesicles including exposing a sample comprising at least one extracellular vesicle to ultrafiltration; and exposing the sample following the ultrafiltration in step (i) to size exclusion liquid chromatography.

The present invention pertains to inter alia methods for purifying extracellular vesicles including exposing a sample comprising at least one extracellular vesicle to ultrafiltration; and exposing the sample following the ultrafiltration in step (i) to size exclusion liquid chromatography.