Living recombinant Saccharomyces cerevisiae secreting proteins or peptides as a new drug delivery system in the gut.
New strategies to prevent or treat diseases have been focusing on innovative approaches, such as the oral administration of living recombinant micro-organisms delivering active compounds in the digestive environment. The survival rate and the ability of two recombinant Saccharomyces cerevisiae strains (WppV(5)H(6) and WppGSTV(5)H(6)) to initiate the synthesis and secrete either a model peptide (peptide-V(5)H(6), MW: 5.6 kDa) or a model protein (glutathione-S-transferase-V(5)H(6), MW: 31.5 kDa) were studied in a gastric-small intestinal system simulating human digestive conditions. The WppV(5)H(6) and WppGSTV(5)H(6) strains respectively showed 83.1%+/-9.6 (n=3) and 95.3%+/-22.7 (n=4) survival rates in the model upper digestive tract after 270 min of digestion. The secretion products were detected as early as 90 min after the yeast intake/gene induction in each compartment of the in vitro system, but mostly in the jejunum and ileum. The GST-V(5)H(6) concentrations in the digestive medium reached 15 ng ml(-1), close to values measured in batch cultures. These results open up new opportunities for the set up of drug delivery systems based on engineered yeasts secreting compounds directly in the digestive tract. The main potential medical applications include the development of oral vaccines, the correction of metabolic disorders and the in situ production of biological mediators.
Blanquet
Stéphanie
S
Equipe de Recherche Technologique 'Conception, Ingénierie et Développement de l'Aliment et du Médicament' (ERT CIDAM), Centre de Recherche en Nutrition Humaine (CRNH), Université d'Auvergne, Faculté de Pharmacie, Clermont-Ferrand, France.
Antonelli
Richard
R
Laforet
Laurent
L
Denis
Sylvain
S
Marol-Bonnin
Sylvie
S
Alric
Monique
M
D000818:Animals; D001483:Base Sequence; D016503:Drug Delivery Systems; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism*; D005818:Genetic Engineering; D005982:Glutathione Transferase / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
D010455:Peptides; D011506:Proteins; D005982:Glutathione Transferase