The present disclosure relates to materials, formulations, production methods, and methods for delivery of CFTR mRNA, including but not limited to chemically modified mRNA for induction of CFTR expression, including in the mammalian lung. The present invention is particularly useful for treating cystic fibrosis, but is also useful in the treatment of diseases related to CFTR gene.

Mucus penetrating nanoparticles for inducing, increasing, or enhancing an immune response typically include core of a blend of a biodegradable hydrophobic polymer and a hydrophilic polymer, wherein ≥50% of the biodegradable polymer is conjugated to the hydrophilic polymer, and the hydrophilic polymers forms a coating on the particle. The particles encapsulate a cargo, typically an antigen, adjuvant or other immunomodulator, or a nucleic acid encoding the antigen, or combination thereof. Pharmaceutical compositions including an effective amount of particles to induce an immune response in a subject in need thereof are also provided. Methods of inducing an immune response are also provided, and typically include administering to a subject, preferably via the respiratory tract, the pharmaceutical composition. In some embodiments, the subject has cancer or an infection of the lung.

Provided are targeted nanoparticles. In certain embodiments, the targeted nanoparticles comprise a nanoparticle and a myeloid cell (MC) targeting moiety stably associated with the outer surface of the nanoparticle. According to some embodiments, the MC targeting moiety is an immunosuppressive myeloid cell (isMC) targeting moiety. In certain embodiments, the targeted nanoparticles further comprise a detectable label (e.g., an in vivo imaging agent), a drug, or both. Also provided are compositions comprising the targeted nanoparticles of the present disclosure. Methods of using the targeted nanoparticles to image MCs (e.g., isMCs) and/or to modulate and/or disrupt MCs (e.g., isMCs) are also provided.

DNA-targeted nanocarriers for encapsulating an active agent and delivering it to extracellular DNA are provided. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. The targeting moiety that targets DNA is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to DNA or nucleosomes. The targeting moiety can be a circulating autoantibody that binds DNA such as those commonly found in patients with SLE. In some embodiments, the targeting moiety is antibody 3E10 or a variant, fragment, or fusion protein derived therefrom. Pharmaceutical compositions, methods of use, and dosage regimens are also provided.

The present invention provides methods and compositions comprising a particle comprising at least one first targeting agent which binds a first target on an NK cell surface, and at least one second targeting agent which binds a second target on a cancer cell surface, wherein the second targeting agent is different from the first targeting agent.

Disclosed are methods and related compositions for concomitantly, locally administering immunosuppressants and doses of therapeutic macromolecules for reducing Type I and Type IV hypersensitivity.

Methods are provided for improving the manufacture and use of pharmaceutical compositions comprising histidine-lysine copolymers and nucleic acids, which spontaneously form nanoparticles when mixed. The flow rate of mixing and the ratio of copolymer to siRNA strongly affect nanoparticle properties, including size and homogeneity of particles, resulting in greater efficacy in delivery to target cells. Further, an acidic pH of the siRNA solution, as well as the addition of acetate or phosphate salt to the histidine-lysine copolymer prior to mixing with the siRNA also contribute to lower nanoparticle diameters and more uniform particles (lower PDI).

The present invention provides novel engineered HCV E2 polypeptide immunogens and related vaccine compositions that display the engineered E2 polypeptides. The invention also provides methods of using such immunogens and vaccine compositions in various therapeutic applications, e.g., for preventing or treating HCV infections.

A composition, and method for a targeted drug delivery is disclosed in treating central nervous system injury, including blast hearing loss, traumatic brain injury (TBI) and the like, by administering a subject with nanoparticle-based minocycline formulations. The formulation contains nanoparticles encapsulating minocycline for neuroprotective effect in TBI. Albumin nanoparticle-based minocycline formulations provide enhanced delivery to brain, and reduced toxicity at minimal dosage for treating a subject suffering from central nervous system injury including blast induced traumatic brain injury (bTBI). Nanoparticle administered at minimal dose in rat blast TBI model crossed blood-brain barrier (BBB) and enhanced therapeutic concentration compared to free minocycline. Provided is an effective and safe minocycline delivery in TBI with minimal or no toxicity for neuroprotective therapy. Studies indicate performance for behavioral (acute and chronic), pathological (chronic) and hearing loss mitigation using the disclosed drug and nanoparticles in rat moderate bTBI model.

A cerium oxide nanocomplex, a composition containing the cerium oxide nanocomplex as an active ingredient, and uses thereof for preventing or treating peritonitis are disclosed. The cerium oxide nanocomplex improves the biomedical stability, biocompatibility, and efficiency of the production process of nanoparticles while maintaining the excellent inhibitory activity against inflammation by applying a biocompatible polymer composed of an optimal combination. The cerium oxide nanocomplex may be used as an excellent therapeutic composition that may greatly improve patients' survival rate by effectively inhibiting inflammatory response and quickly blocking tissue damage at early stage of peritonitis when a radical inflammatory injury occurs because of the penetration of bacteria, foreign body and immune cells into a perforated organ in the abdominal cavity.