The present application describes a two-step drug delivery formulation comprising a high affinity interaction between a drug conjugate and a compound, followed by introduction of a second compound with higher affinity to the drug conjugate to facilitate drug release. Delivery methods and specific interactions are also described.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

Provided are novel recombinant proteins that are capable of self-crystallization and exhibit desirable physical properties such as enhanced cellular uptake or and endoso-mal escape. Polynucleotides encoding the recombinant proteins as well as methods of making and using such proteins are also described.

Provided are novel recombinant proteins that are capable of self-crystallization and exhibit desirable physical properties such as enhanced cellular uptake or and endoso-mal escape. Polynucleotides encoding the recombinant proteins as well as methods of making and using such proteins are also described.

A novel nucleic acid delivery system is provided containing a linear histidine-lysine rich cysteine-containing peptide bearing a targeting function, and a four branched histidine-lysine rich polypeptide. The delivery system includes a nucleic acid, such as an siRNA. The components form a nanoparticle complex through multiple non-covalent interactions between the phosphates of siRNA and histidine/lysine of the polypeptide, with reduced toxicity. The stable complex selectively delivers the genetic material to cells. The targeting function enhances the efficiency of the nucleic acid delivery and transfection.

Carrier molecules also are provided that have the ability to deliver a therapeutic molecule to a specific cell within a tissue in the body. The carrier molecule is modified with a targeting ligand capable of binding to specific receptors present or upregulated on the cell to be targeted. The therapeutic molecule is an siRNA, miRNA, or other oligonucleotide. The targeting moiety is a small molecule, peptide, or protein that shows an affinity for a receptor present on the cell to be targeted.

Bivalent compounds composition comprises one or more of the bivalent compounds. The bivalent compound comprises a cyclic-AMP response element binding protein (CBP) and/or adenoviral EA binding protein of 300 kDa (P300) ligand (CBP/P3000 ligand) conjugated to a degradation tag. The method of using the bivalent compounds is treating certain disease in a subject in need thereof. The method of identifying such bivalent compounds is disclosed.

A method for chemically induced homing of extracellular vesicles (EVs) to a specific tissue or organ in a subject for either treatment or diagnosis of a medical condition, the method comprising administering to the subject an amount of a homing agent. The homing agent is at least one of a derivative of polyethylene glycol), or a derivative of phenothiazine;. The EVs are homed to the homing agent in the subject.

A method for chemically induced homing of extracellular vesicles (EVs) to a specific tissue or organ in a subject for either treatment or diagnosis of a medical condition, the method comprising administering to the subject an amount of a homing agent. The homing agent is at least one of a derivative of polyethylene glycol), or a derivative of phenothiazine;. The EVs are homed to the homing agent in the subject.

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct C.sup.A bound to a Trigger T.sup.R, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct C.sup.A bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct C.sup.A bound to a Trigger T.sup.R, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct C.sup.A bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.