Chapter 7 - Posttranslational Modification of Heterologous Human Therapeutics in Plant Host Expression Systems

Abstract

In recent times, plant molecular farming (PMF) in plant expression hosts has attracted a lot of interest for production of modern human therapeutics. Its advantages include presence of inherent posttranslational modifications, lower cost, safety, ecofriendly, easy scale-up, and fewer regulatory issues. Interestingly, plant hosts impart “natural protection” to human therapeutic recombinant products by default, since they are inherently incapable of harboring/propagating human pathogens. Plants being eukaryotes, it was expected that active versions of human proteins produced within them would resemble natural human proteins. However, it was not found to necessarily be so, owing to inherent differences in the glycosylation patterns of the two hosts. A prerequisite for successful therapeutic applications of PMF-based biopharmaceuticals would be to have them glycosylated in human compatible precise patterns. Glycoengineering technology, wherein the genes of plant specific glycosyltransferases are replaced with their human counterparts, is proving to be a practical approach in modifying the PMF-based products in order to tailor them for human utility. A few such “humanized” products, termed “Biosimilars” and “Biobetters,” actually display the desired effectiveness and functional value. Human Growth Hormone (hGH), surface antigen of Hepatitis B (HBsAg), Hepatitis vaccine ZMapp, and FDA approved enzyme ELELYSO have already been harvested from plant expression systems. This chapter mainly discusses the glycosylation motifs of human biopharmaceutics expressed in plant host systems, the pros combined with cons of using such hosts, the possibility of utilizing plant cell culture, and finally the scope of developing better, cheaper and “humanized” products via glycoengineering methods.