Disclosed are methods and compositions for repolarizing a tumor associated macrophage (TAM) from M2 to M1 comprising administering to a subject in need thereof an effective dose of a compound comprising a dextran backbone and one or more CD206 targeting moieties conjugated thereto. In certain aspects, the compound further comprises a therapeutic agent selected from: paclitaxel, gemcitabine, lapatinib, and doxorubicin. In further aspect, the therapeutic agent comprises a chelator and at least one metal ion. In certain implementations, the at least one metal ion comprises at least one Cu(II) ions.

Disclosed herein, inter alia, are compositions and methods of modulating macrophage activity. Provided is a method of treating a disease (e.g., a macrophage-associated disease, autoimmune disease, inflammatory disease, or a cancer of an organ in the intraperitoneal cavity), the method including intraperitoneally administering to a subject in need thereof a therapeutically effective amount of a nanoparticle composition or pharmaceutical composition. Provided is a silica nanoparticle non-covalently bound to a plurality of nucleic acids, wherein the silica nanoparticle has a net positive charge in the absence of the plurality of nucleic acids. Provided is a pharmaceutical composition including a nanoparticle composition as described herein, and a pharmaceutically acceptable excipient.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Transmembrane protease, serine 6 (TMPRSS6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a TMPRSS6 gene and to methods of preventing and treating a TMPRSS6-associated disorder, e.g., a disorder associated with iron overload and/or a disorder of ineffective erythropoiesis, e.g., hereditary hemochromatosis, β-thalassemia (e.g., β-thalassemia major and β-thalassemia intermiedia), polycythemia vera, myelodysplastic syndrome, congenital dyserythropoietic anemias, pyruvate kinase deficiency, erythropoietic porphyria, Parkinson's Disease, Alzheimer's Disease or Friedreich's Ataxia.

Spherical nucleic acids (SNA) carrying self-aggregating oligonucleotides are described herein. Compositions of the SNA include discrete nanostructures that are not aggregated. Related methods are also described.

The present application provides for a method for controlling coagulation in a subject in need of extracorporeal membrane oxygenation. The method comprises administering an effective amount of an anticoagulant agent that directly inhibits one or more steps in a coagulation pathway to the subject, wherein the effective amount of the anticoagulant agent is capable of controlling coagulation during extra corporeal membrane oxygenation for a coagulation control time of at least 4 hours.

Site-specific modifications of proteins are desirable in biotechnological applications such as biopharmaceuticals, immunotherapy, vaccines, and are useful in chemical biology. Gluconoylation is a non-enzymatic, covalent, post-translational modification commonly observed on N-terminal His-Tags bearing proteins. We synthesized glucono-1,5-lactone derivatives, including azido variants for selective acylation. High yield acylation is achieved by simply mixing derivatives with target protein amidst diverse conditions of temperatures, aqueous buffers, excipients, or complex cell lysate.

Provided are compositions and methods useful in regenerating damaged tissue, especially cardiac tissue, by delivering to the site of injury an miRNA that can reduce, for example, the expression of phosphatase and tensin homolog (PTEN). The compositions and methods of the disclosure may be generally applied to deliver an miRNA to a cell or tissue such as, but not limited to, a neuron, a smooth muscle cell, or a tumor cell. The compositions comprise a transmembrane carrier peptide conjugated, optionally by a linker, to an oligonucleotide complementary to an miRNA. The carrier peptide facilitates the entry of the miRNA into cells and for delivery to a tissue of an animal or human may be mixed with an extracellular matrix-derived hydrogel carrier.

The present application relates to a novel conjugate group linkable to a compound (such as a therapeutic compound), for use in directing the compound to a target in the body. The conjugate group disclosed herein can enable an expression-inhibitory oligonucleotide (such as a RNAi reagent) to target liver cells to regulate gene expression. The conjugate group disclosed herein has a variety of applications when linked to expression-inhibitory oligonucleotides, comprising applications in therapy, diagnosis, target verification, and genome development. A composition comprising the conjugate group disclosed herein can mediate expression of target nucleic acid sequences in liver cells (such as hepatocytes) when linked to expression-inhibitory oligonucleotides, and can be used for treatment of diseases or disorders responding to the gene expression or activity of cells, tissues, or organisms.

Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule, and a second moiety that specifically binds a lysosomal targeting molecule. In certain embodiments, the first moiety is a knottin peptide comprising an engineered loop that binds to the cell surface molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface molecules (e.g., proteins) via the endosomal/lysosomal pathway. Also provided are compositions and kits that include the bifunctional molecules, as well as methods of using the bifunctional molecules. Methods of making bifunctional molecules are also provided.

Provided herein are gene editing systems and/or compositions comprising RNA guides targeting LDHA for use in genetic editing of the LDHA gene. Also provide herein are methods of using the gene editing system for introducing edits to the LDHA gene and/or for treatment of primary hyperoxaluria (PH), and processes for characterizing the gene editing system.