title: Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease.
abstract: Gaucher's disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy (ERT) using recombinant GCD that is administered intravenously every 2 weeks. However, intravenous administration includes discomfort or pain and might cause local and systemic infections that may lead to low patient compliance. An orally administered drug has the potential to alleviate these problems. In this study, we describe the potential use of plant cells as a vehicle for the oral delivery of recombinant human GCD (prGCD) expressed in carrot cells. The in vitro results demonstrate that the plant cells protect the recombinant protein in the gastric fluids and may enable absorption into the blood. Feeding experiments, with rat and pig as model animals, using carrot cells containing prGCD, show that active recombinant prGCD was found in the digestive tract and blood system and reached both, liver and spleen, the target organs in GD. These results demonstrate that the oral administration of proteins encapsulated in plant cells is feasible. Specifically, carrot cells containing recombinant human prGCD can be used as an oral delivery system and are a feasible alternative to intravenous administration of ERT for GD.
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Shaaltiel
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gingis-Velitski
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Salit
authors.initials: S
authors.lastname: Tzaban
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Nadia
authors.initials: N
authors.lastname: Fiks
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Tekoah
authors.affiliation: Protalix Biotherapeutics, Carmiel, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Aviezer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D018938:Caco-2 Cells; D056947:Enzyme Replacement Therapy; D004795:Enzyme Stability; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D009928:Organ Specificity; D059828:Plant Cells / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D034421:Sus scrofa; D014018:Tissue Distribution; D014026:Nicotiana / Q000378:metabolism*; D057900:Transcytosis
chemical_list: D011994:Recombinant Proteins; D005962:Glucosylceramidase
keywords: Gaucher's disease; enzyme replacement therapy; lysosomal storage disorder; oral delivery; plant cells; β-glucocerebrosidase