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

Jayme L. Workinger, Akhila N.W. Kuda-Wedagedara, Mara M. Julin, Jordan M. White, Ebba Nexo, Nerissa T. Viola, Robert Patrick Doyle

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number12269
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Intrinsic Factor
Liver
Stomach
Vitamin B 12
Glycosylation
Ileum
Ear
Gastrointestinal Tract
Kidney
Research
intrinsic factor-cobalamin receptor

ASJC Scopus subject areas

  • General

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Systemically Administered Plant Recombinant Holo-Intrinsic Factor Targets the Liver and is not Affected by Endogenous B12 levels. / Workinger, Jayme L.; Kuda-Wedagedara, Akhila N.W.; Julin, Mara M.; White, Jordan M.; Nexo, Ebba; Viola, Nerissa T.; Doyle, Robert Patrick.

In: Scientific Reports, Vol. 9, No. 1, 12269, 01.12.2019.

Research output: Contribution to journalArticle

Workinger, Jayme L. ; Kuda-Wedagedara, Akhila N.W. ; Julin, Mara M. ; White, Jordan M. ; Nexo, Ebba ; Viola, Nerissa T. ; Doyle, Robert Patrick. / Systemically Administered Plant Recombinant Holo-Intrinsic Factor Targets the Liver and is not Affected by Endogenous B12 levels. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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