Protein cyclization is a method for making proteins more stable. The method requires a properly designed linker to connect the original N-terminus and C-terminus of a protein sequence. A new strategy is used for creating flexibility in the linker design. The new strategy includes an activatable polypeptide arrangement to produce cyclized proteins, characterized in that the strategy can be used to produce cyclized interleukins. The strategy cyclizes the interleukins via introducing a linker into the interleukin and using an intein-mediated protein splicing. The linker sequence is not related to the protein splicing reaction, thus providing flexibility in the introduction of linker. The prepared cyclized interleukins contain high structural stability, native interleukin structure and long-lasting activity. The cyclized interleukins have the potential to replace native interleukins in bio-industrial applications or to modulate the functions of interleukins.

The present disclosure relates to targeted degradation platform technology. For example, the present disclosure relates to bispecific binding agents for degrading endogenous proteins, whether membrane-associated or soluble, using the lysosome pathway. The disclosure also provides methods useful for producing such agents, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various disorders.

Safe, rapid and efficient methods for producing antigen-specific T cells recognizing human papilloma virus or HPV antigens.

Provided herein are novel p62 compositions for the modulation of expression of a proinflammatory cytokines, osteogenic transcription factors, a bone resorptive factors and endogenous p62. Consequently, such p62 compositions are useful for prophylaxis and treatment of inflammatory diseases and related methods. In certain embodiments the inflammatory diseases are not cancer-related. In various embodiments, the inflammatory diseases include, but are not limited to osteoporosis, obesity, metabolic syndrome, type 2 diabetes, fat liver, inflammatory bowel disease, chronic pancreatitis, asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), osteoarthritis, multiple sclerosis (MS), psoriasis, congestive heart failure (CHF), atherosclerosis, neurodegenerative diseases (ALS, Parkinson, Alzheimer's, Huntington disease), depression, schizophrenia, gout, asbestosis and silicosis.

Polypeptides for use in suppressing cancer and cancer disorders and methods of treatment using such polypeptides.

Polypeptides are provided directed against IL-6R at specific dose ranges and dosing schedules that result in a prolonged effect on IL-6 mediated signaling. In particular, the invention provides pharmacologically active agents, compositions, methods and/or dosing schedules that have certain advantages compared to the agents, compositions, methods and/or dosing schedules that are currently used and/or known in the art, including the ability to dose less frequently or to administer lower doses to obtain equivalent effects in inhibiting IL-6 mediated signaling.

Methods of diagnosing infections are disclosed. In one embodiment, the method comprises measuring the amount of each of the polypeptides TRAIL, CRP, IP10 and at least one additional polypeptide selected from the group consisting of IL-6 and PCT.

The described invention provides a method of treating a lung injury at risk of progressing to a fibrotic lung disease in a subject in need thereof comprising administering to the subject a composition comprising a therapeutic amount of IL-6 polypeptide, hyaluronan (HA), mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, wherein the therapeutic amount is effective to increase renewal of alveolar epithelial cell 2 (AEC2) stem cells, to repair the injury, to reduce lung fibrosis, or a combination thereof.

Methods of diagnosing infections are disclosed. In one embodiment, the method comprises measuring the amount of each of the polypeptides TRAIL, CRP, IP10 and at least one additional polypeptide selected from the group consisting of IL-6 and PCT.

Genetically modified non-human animals that are immunodeficient and comprise xenotransplanted hepatocytes such as human hepatocytes, wherein the genetically modified non-human animal and/or the transplanted hepatocytes are modified to restore interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway activity or interleukin-6 receptor subunit beta (GP130) signaling pathway activity in the transplanted hepatocytes, are provided. Also provided are methods of assessing the activity of human-liver-targeting reagents in such non-human animals and methods of making animals with a humanized liver (e.g., with reduced steatosis). Also provided are genetically modified non-human animals comprising an inactivated endogenous Rag2 gene, an inactivated endogenous Il2rg gene, an inactivated endogenous Fah gene, a humanized IL6 gene, and optionally an inactivated endogenous Rag1 gene and methods of using and making such animals. Also provided are methods of reducing or ameliorating hepatosteatosis in non-human animals with humanized livers.