Glycotargeting therapeutics

Abstract

Several embodiments of the present disclosure relate to therapeutic compositions configured to target the liver of a subject and that are useful in the treatment or prevention of one or more of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent. In several embodiments, the compositions are configured to target the liver and deliver antigens to which tolerance is desired. In several embodiments, the compositions are configured for clearance of a circulating protein or peptide or antibody associated with one or more of the above-mentioned maladies. Methods and uses of the compositions for induction of immune tolerance are also disclosed herein.

What is claimed is: 
     
         1 . A method of inducing antigen-specific immune tolerance in a subject, the method comprising:
 administering to a subject a compound comprising:   an peptide to which tolerance is desired;
 wherein the peptide to which tolerance is desired, when presented alone to the subject is capable of inducing an unwanted immune response in the subject; 
   a polymeric linker comprising:
 a copolymer or a random copolymer, wherein the copolymer or random copolymer comprises a first methacrylate unit and a second methacrylate unit, the first methacrylate unit comprising a first ethylacetamido functionality and the second methacrylate unit comprising a second ethylacetamido functionality; 
 wherein the second ethylacetamido functionality is conjugated to an aliphatic group, an alcohol, or an aliphatic alcohol; 
 wherein the polymeric linker is bonded to the peptide to which tolerance is desired via a disulfide bond or a disulfanyl ethyl ester, 
 wherein the disulfide bond or the disulfanyl ethyl ester are each configured to be cleaved upon administration of the compound to the subject and to release the peptide to which tolerance is desired from the polymeric linker; and 
   a liver-targeting moiety;
 wherein the liver-targeting moiety comprises a galactosylating or glucosylating moiety; 
 wherein the liver-targeting moiety is bonded to the polymeric linker through the first ethylacetamido functionality.