Systemically Administered Plant Recombinant Holo-Intrinsic Factor Targets the Liver and is not Affected by Endogenous B12 levels

Abstract

Precision targeting imaging agents and/or treatment agents to select cells or organs in the body remains a significant need and is an area of intense research. It has been hypothesized that the vitamin B12 (B12) dietary pathway, or components thereof, may be exploitable in this area. The question of whether gastric Intrinsic factor (IF), critical for B12 absorption in the GI tract via the cubilin receptor, could be used as a targeting moiety for the cubilin receptor systemically, has not been investigated. Cubilin is the only known receptor for holo-IF and is found primarily in the kidney and ear (outside of the ileum of the GI) offering significant scope for specific targeting. We utilized plant derived human gastric IF in fluorescent cell and PET based in vivo imaging and biodistribution studies and demonstrated that plant derived IF primarily targets the liver, likely a consequence of the unique glycosylation profile of the IF, and is not affected by endogenous B12 levels.