The present invention relates to a multi-specific binding conjugate, a related composition and use. The binding conjugate comprises binding moieties for two or more different receptors, co-receptors, antigens or cellular markers which moieties are coupled by a nanomaterial. The multi-specific binding conjugate can be used to modulate an immune response, treat or prevent a disease or condition (e.g., a cancer, autoimmune disease, pathogen infection or inflammatory disease).

Disclosed are synthetic nanocarrier compositions, and related methods, comprising therapeutic protein APC presentable antigens and immunosuppressants that provide tolerogenic immune responses specific to therapeutic proteins.

Disclosed are synthetic nanocarrier compositions, and related methods, comprising immunosuppressants and MHC Class II-restricted epitopes of an allergen that provide tolerogenic immune responses specific to the allergen.

Compositions for enhanced gene editing and methods of use thereof are. The composition contains a cell-penetrating antibody and a donor oligonucleotide containing a sequence that can correct a mutation in a cell's genome. Preferably, the composition does not contain a nuclease, PNA, or nanoparticle. The compositions are used to modify the genome of a cell by contacting the cell with an effective amount of the composition. Genomic modification occurs at a higher frequency both ex vivo and in vivo, when cells are contacted with the cell-penetrating antibody and donor oligonucleotide as compared to the absence of the cell-penetrating antibody.

An immunomodulatory delivery system includes a hydrogel, a first immunomodulatory cargo encapsulated in the cargo, and a second immunomodulatory cargo encapsulated in the hydrogel. The hydrogel includes a polymer non-covalently crossed-linked with a plurality of nanoparticles. The first immunomodulatory cargo is smaller than the second immunomodulatory cargo. A ratio of a diffusivity of the first immunomodulatory cargo through the hydrogel to a diffusivity of the second immunomodulatory cargo through the hydrogel is less than 3.

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).

Disclosed are synthetic nanocarrier compositions, and related methods, comprising immunosuppressants and MHC Class II-restricted epitopes of an allergen that provide tolerogenic immune responses specific to the allergen.

Provided are therapeutic compositions, comprising: a polymeric nanoparticle; a ligand selected to activate an EGFR receptor; and a linker, the linker associating the nanoparticle and the ligand. Also provided are therapeutic compositions, comprising: a nanoparticle; a ligand, the ligand being any one of EGF, transforming growth factor-alpha (TGFα), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), or epigen; and a linker associating the nanoparticle and the ligand, the therapeutic composition having a surface charge in the range of from about −5 to about 30 mV. Related methods of treatment are also provided.

This invention provides methods for producing a polymer particle which contains unusually high negative charges on the surface of the particle. Preferably, the polymer is pharmaceutically acceptable. The negative charges can be conferred by chemical groups such as carboxyl, sulfonate, nitrate, fluorate, chloride, iodide, persulfate, and many others, with carboxyl group being preferred. The invention also provides polymer particle produced by the methods of the invention.

The disclosure provides, among other things, compositions that bind to and inhibit the biological activity of soluble biomolecules, as well as pharmaceutical compositions thereof. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.