Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

An experiment has shown that ranpirnase is a microbicide. It is believed that topical application of a topical pharmaceutical composition consisting essentially of a prophylactically effective concentration of an enzymatically-active ribonuclease (e.g. ranpirnase) and a viscous vehicle that does not unacceptably interfere with the enzymatic activity (e.g. K-Y® Brand Jelly) will prophylactically protect an individual from a sexually-transmitted viral infection, particularly HIV. It is also believed that e.g. ranpirnase can be delivered to tissues of an individual who is to be prophylactically protected against viral infections by transfecting ranpirnase DNA into human microbiota and exposing the individual to the thus-modified human microbiota. It is also believed that ranpirnase can be delivered to a woman who is to be prophylactically protected against a sexually-transmitted viral infection by use of an intravaginal ring that has been impregnated with ranpirnase.

Disclosed are cell membrane-derived nanovesicles, a method of preparing the nanovesicles, and a pharmaceutical composition and a diagnostic kit using the nanovesicles. The cell membrane-derived nanovesicles may prevent potential adverse effects because intracellular materials (e.g., genetic materials and cytosolic proteins) unnecessary for delivering therapeutic or diagnostic substances are removed from the nanovesicles. In addition, as the nanovesicles may be targeted to specific cells or tissues, therapeutic or diagnostic substances may be predominantly delivered to the targeted cells or tissues, while delivery of the substances may be inhibited. Therefore, the nanovesicles may alleviate suffering and inconvenience of patients by reducing adverse effects of therapeutic substances and by improving efficacy of the substances. In addition, the cell membrane-derived nanovesicles loaded with therapeutic or diagnostic substances and a method of preparing the nanovesicles may be used in vitro or in vivo for therapeutic or diagnostic purposes, or for experimental use.

Disclosed herein are improved nanozymes for targeting RNA. The disclosed nanozymes are synthesized using recombinant RNase A with site-specific cysteine-substituted mutations that can be covalently functionalized with a length-tunable multi-thiol tether and then loaded onto gold particles through multiple gold-sulfur bonds. This new RNase A loading mechanism is site specific, and it allows high-density loading of alkylthiol modified DNA oligonucleotides. The disclosed nanozymes can also include additional capturer strands and/or involve DNA-recombinant-RNase-A unibodies to further increase the nanozyme's enzymatic activity and target selectivity. Also disclosed are functional on-off switchable nanozymes to control nanozyme activity. In some embodiments, the disclosed nanozyme are core-free hollow forms. The removal of the inorganic nanoparticle cores from nanozymes can effectively eliminate the potential long-term toxicity induced by the core, and also creates a cavity for loading and delivery of small molecule drugs.

Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.

A nanocomplex containing a delivery agent and a pharmaceutical agent. The nanocomplex has a particle size of 50 to 1000 nm, the delivery agent binds to the pharmaceutical agent via non-covalent interaction or covalent bonding, and the pharmaceutical agent is a modified peptide or protein formed of a peptide or protein and an added chemical moiety that contains an anionic group, a disulfide group, a hydrophobic group, a pH responsive group, a light responsive group, a reactive oxygen species responsive group, or a combination thereof.

The present disclosure provides methods of treating paroxysmal nocturnal hemoglobinuria (PNH) in subjects with varying exposure to eculizumab by administering R5000. The methods include methods of switching subjects from treatment with eculizumab to R5000.

A method of producing plant virus-like particles includes freeze drying an aqueous solution of plant virus particles to produce a substantially RNA-free plant virus-like particles.

The present invention relates to conjugates of a protein drug and two or more P/A peptides, and pharmaceutical compositions comprising them. The conjugates of the invention exhibit an advantageously reduced immunogenicity as compared to the respective unmasked protein drugs as well as a favorable safety and tolerability profile, which render them particularly suitable for therapeutic use. The conjugates further show an enhanced plasma half-life and, thus, a prolonged duration of action as compared to the respective unmasked protein drugs, which allows for a reduction in the dosing frequency and, thus, side-effect burden. The invention also provides processes of preparing such conjugates as well as activated P/A peptides that are useful as synthetic intermediates in the preparation of the conjugates.

A composition including porous silica particles according to an embodiment of the present invention may effectively deliver a bioactive material to target tissues or cells in the blood stream by modifying surfaces of the particles to inhibit aggregation and precipitation in the blood. An embolic composition including the composition may have an advantage of having specific physical properties such as biodegradability and sustained release thus to achieve excellent embolization effects and targetability toward target tumor tissues or cells, thereby reducing side effects.