Genetically modified corn could soon be used to mass-produce the enzymes used in rare-disease therapies, according to new research.
The study, published in Nature Communications, focussed on alpha-L-iduronidase – the bone and tissue building enzyme mucopolysaccharidosis I (MPS I) patients are missing, known as a lysosomal storage disease (LSDs).
Ordinarily, the enzyme used in therapy for MPSI would be created by culturing mammalian cells – a difficult and costly process. However, researchers believe a new transgenic maize could do the job cheaply and more easily.
If successful, the team – led by Allison Kermode, a plant biologist at Simon Fraser University in Canada – believe the process could replace the current one, which costs hundreds of thousands of dollars each year per patient.
“From the point of view of recombinant protein production platforms, the current production systems for enzyme replacement therapy (ERT) and the resultant enzyme therapeutics have some drawbacks that justify an examination of potential alternatives,” Kermode wrote.
She added that though there is currently little commercial interest in rare LSD indications because of the high-cost-low-patient ratio, the lower cost method could gain more attention for the area.
How it works
Expressing human proteins – like enzymes – is notoriously difficult in plant cells because they usually pick up a coating of sugar molecules – known as glycosylation – which could be potentially toxic in vivo.
However, through a unique mRNA (messenger ribonucleic acid) targeting strategy through genetic modification of the endosperm storage tissue of the maize seeds, the researchers successfully controlled glycosylation of the alpha-L-iduronidase enzyme.
The team believe the method is successful because instead of modifying the human protein – which often changes the way it functions – they simply stopped the plant from adding sugars.
The tech is one of the first to successfully mass-produce safe human enzymes in plants, besides the recently Food and Drug Administration (FDA) approved enzyme Elelyso (taliglucerase alfa) for Gaucher disease; another LSD.
However the team believes it could be the first step in a new cheaper and safer production technique for a wide array of proteins.
“Safety concerns associated with product contamination included the recent and highly publicised viral contamination of the chinese hamster cell (CHO) cell cultures at Genzyme Corporation, which resulted in interrupted or dosereduced treatments, or the initiation of alternative treatments,” Kermode et al said.
“Perhaps also of importance, there is considerable Nglycan heterogeneity and variability of glycoforms of a recombinant protein depending on the CHO cell culture conditions of possible relevance to immunogenicity issues.”
The team said plant and seed-based systems could be an alternative with minimal risk of contamination by human pathogens or prions, and when developed could rapidly increase biomass without the need for pricey fermentation costs.
“Maize as a host for recombinant protein production has considerable advantages, including the highest biomass yield among seed crops, ease of transformation and scaleup and the availability of strong promoters and other gene regulatory sequences to facilitate highlevel recombinant protein production,” Kermode added.