Endogenous intrinsic factor (IF) is a glycoprotein in humans that is synthesized and secreted by the parietal cells of the stomach. It has a sole and crucial function of binding and transporting ingested sources of vitamin B12 to the specific IF-B12 receptor, cubilin, in the terminal ileum where the B12 is absorbed and released for transport in the bloodstream. Intrinsic factor is essential for the normal physiological uptake of vitamin B12 as the cubilin receptor recognizes only the intrinsic factor when bound to B12 but neither intrinsic factor nor free B12 alone.
Historically, exogenous supply of intrinsic factor has generally been limited to being sourced from the stomach or intestine of animals, or directly from human gastric juice. Both sources have inherent disadvantages due to possible pathogen transmission and contamination by native corrinoids (either cobalamin or cobalamin analogues), or by other cobalamin-binding proteins (haptocorrin) that cannot be completely removed, thereby limiting the purity and functionality of the IF.
Moreover, the feasibility of supplying sufficient intrinsic factor from these sources for use in a therapeutic dosage form has proved inefficient, cost prohibitive, and has led to the scarcity and all but complete disappearance of the Schilling’s diagnostic test for B12 deficiency.
Unlike animals or humans, plants do not have any metabolic use for vitamin B12 and do not produce it. Consequently, plants offer the most suitable vehicle for producing a commercially viable form of pure and unbound IF (apoIF) that is free from contamination or exposure to IF binding corrinoids.
Xeragenx produces a purified recombinant human intrinsic factor (rhIF) that is transgenically expressed in the plant Arabidopsis thaliana. The protein has been shown to bind B12 correctly and in turn bind to the cubilin receptor with as good or better affinity than human IF.