The combined actions of Fc-AK183-mediated cleavage and subsequent renal clearance of IgA resulted in a lasting obliteration of blood IgA, as demonstrated in a human IgA-injection model and in a humanized α1KI transgenic model. Fc-AK183 was also able to remove chronic IgA and associated complement C3 deposits in the glomerulus.

Our study focused on the construction and testing of a long-acting IgA protease for the treatment of IgAN. We selected bacterial IgA protease AK183 as the template and followed an Fc-fusion strategy to extend the in vivo t 1/2 of the therapeutic enzyme.

2002年4月5日 · C. ramosum strain AK183, which produces an IgA proteinase that cleaves both human IgA1 and the IgA2m (1) allotype, was obtained from Dr. Y. Fujiyama (Kyoto, Japan). Bacteria were grown anaerobically at 37 °C in 2× YT medium (14) supplemented with 0.05% sodium thioglycolate.

2022年3月28日 · In mice injected with human IgA and in a humanized mouse model of IgA nephropathy, this protease, termed Fc-AK183, cleared IgA from the circulation and cleared deposits of IgA and associated...

Bacterial Strains—C. ramosum strain AK183, which produces an IgA proteinase that cleaves both human IgA1 and the IgA2m(1) allo- type, was obtained from Dr. Y. Fujiyama (Kyoto, Japan).

2020年1月20日 · To detect Gd O-glycan attachment sites, purified IgA1 proteins were treated with an IgA-specific protease from Clostridium ramosum AK183 (a recombinant enzyme produced in Escherichia coli) 37...

The combined actions of Fc-AK183-mediated cleavage and subsequent renal clearance of IgA resulted in a lasting obliteration of blood IgA, as demonstrated in a human IgA-injection model and in a humanized a1KI transgenic model.

We chose an IgA protease of commensal bacterium Clostridium ramosum, termed AK183, as the template for constructing a recombinant biologic. To extend the t 1/2 in blood, we fused AK183 to the Fc segment of human IgG1.

Fc-AK183 was also able to remove chronic IgA and associated complement C3 deposits in the glomerulus. We constructed a chimeric fusion of IgA protease with Fc and demonstrated its long-lasting efficacy as a promising targeted therapy for IgA nephropathy in mouse models.

2022年2月16日 · Methods: We chose an IgA protease of commensal bacterium Clostridium ramosum, termed AK183, as the template for constructing a recombinant biologic. To extend the half-life in blood, we...