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Doctoral thesis, 2020

Production of human heme-binding proteins in plants for potential pharmaceutical and nutritional uses

Carlsson, Magnus ;

Abstract

Plants have a long history as a source of nutrition and medication. In the last few decades, interest has also emerged in using plants as a production system for protein pharmaceuticals, in part due to possible scale-up- and safety-benefits with this method of production. One class of protein pharmaceuticals for which the use of a plant production system might be particularly interesting is hemoglobin-based oxygen carriers (HBOC’s), a type of pharmaceutical intended to function as an alternative to donated blood in clinical situations. HBOC’s face many safety and production challenges, that have so far prevented widespread use, and production in plants could perhaps help towards solving these problems. In this thesis, we aimed to express and characterize proteins of interest with the goal of using them in oxygen therapeutics, using transient expression in Nicotiana benthamiana. The expressed recombinant proteins were based on human myoglobin (Mb), fetal hemoglobin (HbF) and α1-microglobulin (A1M). The proteins were successfully expressed in tobacco leaves and the purified proteins displayed their respective functional activity. The plant expression system thus showed its efficacy, and was capable of supplying the critical heme for Mb and Hb production, something that may also have implications for using plants as a source of nutritional iron. While more work is needed, the results help to show the feasibility of using heme-binding proteins produced in plants for pharmaceutical uses, something that was also underlined by animal- and cell-tests.

Keywords

Molecular farming; heterologous expression; transient expression; oxygen therapeutic; HBOC; hemoglobin; myoglobin; α1-microglobulin; A1M; XTEN

Published in

Acta Universitatis Agriculturae Sueciae

2020, number: 2020:34
ISBN: 978-91-7760-586-7, eISBN: 978-91-7760-587-4
Publisher: Swedish University of Agricultural Sciences, Department of Plant Breeding

Authors' information

Carlsson, Magnus (Carlsson, Magnus )
Swedish University of Agricultural Sciences, Department of Plant Breeding

UKÄ Subject classification

Other Medical Biotechnology
Plant Biotechnology
Biochemistry and Molecular Biology

URI (permanent link to this page)

https://res.slu.se/id/publ/105512