Production of an edible drug for multiple sclerosis treatment in tomato fruit — ASN Events
  1. Schedule
  2. SESSION 8: Innovations in peptide science
  3. Production of an edible drug for multiple sclerosis treatment in tomato fruit

Production of an edible drug for multiple sclerosis treatment in tomato fruit (#44)

Linh T.T. Nguyen 1 , Mark A. Jackson 1 , Edward K. Gilding 1 , Kuok Yap 1 , Brett R. Hamilton 2 , David J. Craik 1
  1. Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, St Lucia, Brisbane, Queensland, Australia
  2. Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia, Brisbane, Queensland, Australia

Multiple sclerosis (MS) is a chronic autoimmune disease that attacks the central nervous system leading to progressive neurological disability. A single amino acid variant of the plant cyclotide kalata B1, [T20K]kB1, is currently under development as a peptide therapeutic candidate for the treatment of MS symptoms.1 This peptide has shown promising results in both preclinical trials and in a phase I clinical trial.2 Cyclotides are highly stable molecules due to their backbone cyclization and three disulfide bonds, thus these qualities support the oral delivery of these molecules.3 In this study, we exploited the advantages of both plant-based production system and oral drug delivery route by producing [T20K]kB1 in tomato fruits which could potentially be used as an edible drug for MS treatment. In this approach, the peptide would not need to undergo costly and yield-reducing downstream processing. By co-integrating the [T20K]Oak1 precursor and CtAEP1 gene into tomato genome, we demonstrated the successful production of cyclic [T20K]kB1 to yield of 94.45 ± 8.65 µg/g fruit dry weight. Interestingly, by using MALDI mass spectrometry imaging, we observed the distribution of mature cyclic [T20K]kB1 in the epidermis and structures resembling vascular tissue of the tomato fruit,  linear [T20K]kB1 was observed in a similar pattern to the cyclic form but in a more diffuse pattern. Incomplete products were detected diffusely in the mesocarp and columella. These exciting preliminary results inform the next steps to enhance the production of edible drugs in planta.

References

1 C. Gründemann, K.G. Stenberg, and C.W. Gruber, Int J Pept Res Ther, 2019, 25, 9–13;

2 https://cyone.com/en/projects/multiple-sclerosis;

3 K. Thell, R. Hellinger, E. Sahin, P. Michenthaler, M. Gold-Binder, T. Haider, M. Kuttke, Z. Liutkevičiūtė, U. Göransson, C. Gründemann, G. Schabbauer and C.W. Gruber. Proc Natl Acad Sci U S A, 2016, 113, 3960-3965.

#AusPeptide2023