Anti-HER2 biparatopic antibody-drug conjugates (ADCs) in which the drug is an auristatin analogue and is conjugated to the antibody at a low average drug-to-antibody ratio (DAR), and methods of using the ADCs in the treatment of a HER2-expressing cancer. The low average DAR (<3.9) ADCs as described herein have improved tolerability and decreased toxicity as compared to a corresponding ADC having a DAR ≥3.9 when administered at the same toxin dose.

Provided herein are nucleic acids for expressing modified ligand-gated ion channel proteins in excitable cells or secretory cells, such as nerves and neurons and optionally including viral sequences, such as Adeno-associated virus sequences, for delivery to excitable cells or secretory cells of a patient. Also provided herein are methods of modulating cell membrane potentials in an excitable cell or secretory cell, and for treatment of a disease or disorder associated with the nervous system in a patient, such as chronic pain or itch.

Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule or extracellular molecule, and a second moiety that specifically binds a lysosomal targeting molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface and extracellular 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.

The present invention relates to a targeting-type capsule for drug delivery systems. The present invention addresses the problem of providing a capsule for drug delivery systems by utilizing the reactivity of a thiol with an alkyl halide, wherein the capsule comprises a silole-containing carbosilane dendrimer and a labeling protein containing a target recognition site (e.g., green fluorescent protein), can include a biological polymer or another molecule therein, and can deliver the biological polymer or the like selectively into a target cell.

An IL-15 super agonist (IL-15N72D:IL-15RαSU/IgG1Fc; N-803) increases circulating NK cells, effector memory and effector memory RA cells in post-allogeneic hematopoietic stem cell transplant patients (HCT). Methods of treatment include administration of N-803 to subjects in need of such treatment.

The present disclosure relates to methods and compositions for preventing and/or treating liver fibrosis, liver cancer, and/or liver disease. In particular, the present disclosure relates methods and compositions which to decrease or inhibit microRNA found to be upregulated in liver fibrosis, liver cancer, and/or liver disease, or increase or activate microRNA found to be downregulated in liver fibrosis, liver cancer and/or liver disease. The present disclosure also relates to the use of engineered exosomes or extracellular vesicles in the methods and compositions for targeted delivery of the agents to the liver.

The invention relates to binding molecules that bind specifically to prostate specific membrane antigen (PSMA), in particular, single human variable heavy chain domain antibodies and related methods for treatment of cancer.

Provided herein are engineered cells, comprising: a chemical or biological moiety covalently bound to a cell surface glycan, wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody. Also provided are compositions comprising these engineered cells and methods of making and using the same.

A conjugate may comprise a first component capable of binding to a therapeutic target in the eye, one or more second component(s) capable of binding to hyaluronan, and one or more third component(s) comprising hyaluronan, wherein each second component is covalently bound to the first component and non-covalently bound to a third component, a composition comprising the conjugate for use as a medicament or for use in the treatment of an eye disease and a method of treating an eye disease in a subject. Additionally, a therapeutic molecule targeted to a tissue in a patient may comprises a hyaluronic acid binding moiety and a therapeutically active agent, wherein the hyaluronic acid binding moiety comprises at least two link domains of Versican.

Described herein are cell-free therapeutic compositions derived from blood or plasma and uses thereof for the treatment of selected diseases and disorders.