Use of polymer conjugates for the intraperoxisomal delivery of engineered human alanine:glyoxylate aminotransferase as a protein therapy for primary hyperoxaluria type I

Primary hyperoxaluria type I (PH1) is a rare disease caused by mutations in the AGXT gene encoding the alanine:glyoxylate aminotransferase (AGT) enzyme. AGT deficiency leads to glyoxylate accumulation and the consequent formation of insoluble oxalate crystals throughout the body. We assessed conjugation of AGT to poly(ethylene glycol)-co-poly(L-glutamic acid) (PEG-PGA) block-co-polymers as a potential treatment strategy. The obtained PEG-PGA-AGT conjugates were internalized in a cellular model of PH1 and could reach the correct subcellular compartment. These data hold promise for the development of polyglutamate-based AGT conjugates as a therapeutic option for PH1 patients.262