The present disclosure provides FGF1 mutant proteins having one or more mutations in the heparin binding domain. Such mutants may also have an N-terminal deletion, point mutation(s), or combinations thereof. In some examples, the mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. The disclosed FGF1 mutants can reduce blood glucose in a mammal, and in some examples are used to treat a metabolic disorder.

The present invention relates to a pharmaceutical composition for treating a cancer or an infection in a subject by administrating an amount of an IL-15 derivative conjugate so as to induce a proliferation of natural killer cells (NK cells) which is the same or higher than the one obtained with high dose of interleukin-2 (HDIL-2); eventually associated with a pharmaceutically acceptable carrier.

A new, stable trimeric TNFα structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNFα/TNFR1 interaction. Membrane-bound TNFα is not affected in its ability to signal through TNFR2, and thus the new structure of TNFα may be used in therapies which do not significantly raise the risk of infection or malignancy.

Activated iNKT cells act as senolytic agents, removing senescent cells from target tissues, organs, and compartments of the body. Provided are methods of clearing pathological accumulations of senescent cells by administration of iNKT cell activators such as an alpha-galactosylceramide, or variants or by the adoptive transfer of iNKT cells or precursors, enabling the treatment of senescence-associated conditions such as diabetes, lung fibrosis, and other conditions.

The present disclosure provides conjugates and systems for modulating the activity of a ligand-binding polypeptide such as a D1 dopamine receptor. The present disclosure provides methods of modulating the activity of a D1 dopamine receptor. The present disclosure provides methods of treating Parkinson’s disease in an individual.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class of chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect in the subject.

The present invention provides dendrimer conjugates. The present invention provides a composition comprising a dendrimer conjugate and a cell, such as a cell covered with dendrimer conjugates, in which dendrimer conjugates home the cell to a target tissue.

The present invention relates in a first aspect to a method of coating surfaces of substrates with a lattice-like structure. In particular, the present invention relates to an in vitro method of coating surfaces by binding of epsin or a fragment thereof on the surface and, thereafter, binding of a compound forming the lattice like structure, in particular, binding of the clathrin heavy chain, to the epsin bound on the surface, thus, obtaining a coated substrate having a lattice like structure on the surface. In another aspect, the present invention relates to an in vitro method of producing nanometer-sized liposomes having a clathrin structure on its surface. In addition, substrates, like elements or devices, with coated surfaces having a lattice-like structure on the surface are provided obtainable by a method according to the present invention.

In certain aspects the invention provides a selection of HIV-1 envelopes suitable for use as immunogens, and methods of using these immunogens to induce neutralizing antibodies. In certain embodiments, the immunogens are designed to trimerize. In other embodiments, the immunogens comprise an immune modulating component.

Hypoimmunogenic induced pluripotent stem cell (iPSC)-derived biomimetic nanovesicles (Hypo-BioNVs) or Hypo-exosomes including tailored chimeric antigen receptor (CARs) which can recognize target biomarkers through an antibody fragment scFV region, bifunctional or ByTE antibodies, by a viral epitope recognition receptor (VERR), V.sub.HH nanobody, Variable New Antigen Receptor (V.sub.NAR), engineered TCR, or by any single heavy chain IgG fragment from which a variable region can be engineered. A method of making Hypo-BioNVs. A method of treating an individual with cancer, by administering the Hypo-BioNVs to an individual, targeting cancer cells, and treating the cancer. Hypo-BioNVs including tailored CARs which can recognize target biomarkers through a VERR including viral receptors of an oncolytic virus. A method of treating an individual with cancer, by administering Hypo-BioNVs including CAR receptors having a VERR, V.sub.HH nanobody, V.sub.NAR, engineered TCR, or by any single heavy chain IgG fragment from which a variable region can be engineered with viral receptors of an oncolytic virus to an individual, targeting cancer cells, and treating the cancer. A method of targeting cells in an individual, by administering the Hypo-BioNVs to an individual, and targeting cells to be destroyed or treated for cancer tumors (both liquid and solid), infectious disease, hereditary conditions, autoimmune disease, or metabolic disorders.