Additionally, relatively routine molecular methods have become available for placing the genes of interest into plant expression vectors and transforming them into plants (see Figure 1). Open in a separate window Figure 1 Diagrammatic illustration of the process of Herb Molecular Farming (PMF). An example of an early proof of concept for PMF is the production of plant-derived edible human vaccines, using leafy plants or fruits [30,31,32,33,34,35]. and health supplements.  later expressed the hepatitis B surface antigen (HBsAg) in transgenic tobacco. This plant-derived antigen was actually and antigenically similar to the HBsAg obtained from human serum and recombinant yeast. The yeast-derived HBsAg is usually clinically utilized for HBV vaccination. Since 1994, more than 100 pharmaceutical proteins have been expressed and characterized in plants. By 2011, more than twenty PMF pharmaceuticals were placed in preclinical or clinical trials . Several PMF products have completed Phase 2 trials and one product has been approved by the FDA (Table 1). Although several plant-derived UR 1102 drugs have been commercialized as research and diagnostic reagents (such as tobacco derived aprotinin and rice derived lysozyme from Sigma-Aldrich Company (St. Louis, MO, USA) or received USDA approval as a vaccine additive for use in poultry (Dow Agro Sciences, Indianapolis, IN, USA) , the current review mainly focuses on PMF in relation to human pharmaceutical applications. Plants represent a promising system for the production of human pharmaceutical proteins on a large scale, and at a low cost. Many production challenges, however, such as low yield [7,8,9,10], plant glycosylation [11,12,13], purification and downstream processing hurdles [14,15,16], have limited the development of PMF-based human pharmaceuticals on a clinical scale. In May 2012, the first PMF-derived enzyme, ELELYSO? (taliglucerase alfa) (Protalix BioTherapeutics, Karmiel, Israel), was approved for human use by the Rabbit polyclonal to APEH FDA . ELELYSO? is based on the use of carrot cells to produce recombinant taliglucerase alfa, which is used in an enzyme replacement therapy to treat adult patients with Gaucher disease. The production and application of ELELYSO?, however, is not representative of other PMF-derived pharmaceuticals for several reasons. Since Gaucher disease is a rare genetic disease, mostly found among Ashkenazi Jews, ELELYSO? has limited production needs. The FDA also accelerated (fast tracked) the approval process as a treatment for a rare disease. Additionally, the drug is produced in carrot cells using a large bioreactor under very stringent conditions. This process is different from production of other PMF products, which generally use entire leaves, fruits, seeds, or whole plants to produce the recombinant pharmaceutical. The production and approval of ELELYSO? still represents a major step forward for the whole field of PMF. Many companies have now explored and started product pipelines utilizing plant-expression systems (see Table 2). Table 2 Examples of companies utilizing PMF to produce human pharmaceuticals (data from company websites). leavesVaccine for non-Hodgkins LymphomaMagnICON Transient expressionSpeed and PersonalizationVentria Bioscience, Junction City, KS, USARice seedsVEN150 for HIV-associated chronic inflammationExpress Tec Stable ExpressionScale CostGreenovation Biotech GmbH, Heilbronn, GermanyMossMoss-GAA for Pompe Disease, Moss-GBA for Gauchers Disease, Moss-AGAL for Fabry DiseaseMoss based BroytechnolgySpeed Scale and CustomizedKentucky BioProcessing, Owensboro, KY, USAleavesContract serviceGeneware Transient expressionSpeedPhycoBiologics Inc. Bloomington, IN, USAAlgaeVaccines Growth Factor and enzymesMicroalgae expressionSpeed ScaleMedicago, Qubec, QC, CanadaAlfalfaVaccine for influenza, Pandemic market, Rabies and RotavirusProficia? Transient Expression; Stable ExpressionSpeedSynthon, Nijmegen, The NetherlandsDuckweed LeafyBiomassAntibody for non-Hodgkins LymphomaLEX system Stable expressionSpeed QualityFraunhofer IME, Aachen, GermanyTobacco leavesHIV AntibodyStable Nuclear ExpressionScale CostFraunhofer CMB/iBio, Newark, DE, USAleavesInfluenza vaccineTransient expressionSpeedHealthgen, Wuhan, Hubei, ChinaRice seedSerum albuminStable ExpressionQuality ScalePlanetBiotechnology, Hayward, CA, USATobacco leavesCaroRx for dental caries; PBI-220 antibody for anthrax; DPP4-Fc for MERS coronavirus infectionStable UR 1102 ExpressionQuality Scale Open in a separate window Identifying potential genes suitable for PMF and general approaches is becoming more simple and straight forward. Facilitated by the rapid progress in genomics, proteomics, and bioinformatics, a greater number of useful genes are being identified and characterized. Additionally, relatively routine molecular UR 1102 methods have become available for placing the genes of interest into plant expression vectors and transforming them into plants (see Figure 1). Open in a separate window Figure 1 Diagrammatic illustration of the process of Plant.
- 4 EGFR-targeted nanobodyCPS conjugates localize in tumors specifically
- Similarly, during acute VL, human PBMCs failed to develop IL-1 in response to the stimulation of the antigen (Elliott et?al
- FITC- and Cy3-conjugated supplementary antibodies were utilized to visualize the tagged ORF65 and TGN46 protein, respectively
- Dedication of CIV-DP To measure CIV-DP concentrations, a sandwich ELISA was used
- (D) (Left) Schematic representation of the apoptotic signal induced by Fas-Ab and the antiapoptotic signal induced by Met activation