The therapeutic value of delivering recombinant uricase
to human
patients has been appreciated for decades. The development of therapeutic
uricases has been hampered by the fact that humans do not encode an
endogenous uricase and therefore most recombinant forms of the protein
are recognized as foreign by the immune system and are therefore highly
immunogenic. In order to both shield and stabilize the active enzyme,
we encapsulated a functional ancestral uricase in recombinant, noninfectious
Qβ capsid nanoparticles and characterized its catalytic activity.
Oral delivery of the nanoparticles moderated key symptoms of kidney
dysfunction in uricase-knockout mice by lowering uric acid levels.
Histological kidney samples of the treated mice suggest that delivery
of recombinant uricase had a protective effect against the destructive
effects of uric acid that lead to renal failure caused by hyperuricemia.