Provided herein are compositions including peptide or nucleic acids encoding peptides and related methods for the treatment of angiogenic conditions such as cancer, vascular disorders such as cardiovascular disorders, and infectious disease.

Compositions and methods are provided for the treatment or prevention of chemotherapy-induced peripheral neuropathy and hearing loss in a subject in need thereof. The methods involve administering to the subject a bclw protein, a BH4 domain-containing fragment thereof, or a bclw mimetic. Also provided are exemplary bclw mimetics.

Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.

Methods and FSP27 compositions for treating and/or preventing metabolic disease and conditions associated insulin resistance, obesity, inflammation and dyslipidemia are described.

The present invention relates to peptides comprising analogues of VDAC1-derived peptides having improved pharmacokinetic characteristics compared to the native parent peptides, which are effective in impairing cell energy production, in inducing apoptosis and cell death, particularly of cancerous cells, in eliminating cancer stem cells and in reducing symptoms associated with fat accumulation in liver cells particularly with nonalcoholic fatty liver disease (NAFLD) and symptoms associated thereto.

The present invention relates to TWEAK-receptor agonists for use in the treatment of a cancer, wherein the TWEAK-receptor agonist is combined with immunotherapy of the cancer. The TWEAK-receptor agonist preferably is a multivalent ligand that causes clustering of TWEAK-receptors at the cell surface. A suitable TWEAK-receptor agonist is an agonistic anti-Fn14 antibody. The TWEAK-receptor agonist and immunotherapy be can further be combined with a SMAC mimetic in the treatment of cancer. The TWEAK-receptor agonist is useful, optionally in combination with a SMAC mimetic, to prevent resistance of a cancer to immunotherapy and/or to treat a cancer comprising tumor cells that are resistant to immunotherapy.

Provided herein are lasso peptides libraries, and particularly phage display libraries of lasso peptides. Also provided herein are related methods and systems for producing the libraries and for screening the libraries to identify candidate lasso peptides having desirable properties.

Compositions and methods are provided for the treatment or prevention of chemotherapy-induced peripheral neuropathy and hearing loss in a subject in need thereof. The methods involve administering to the subject a bclw protein, a BH4 domain-containing fragment thereof, or a bclw mimetic. Also provided are exemplary bclw mimetics.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).