Expression and functional evaluation of biopharmaceuticals made in plant chloroplasts

Current Opinion in Chemical Biology

Volumn 38, Issue , 2017, Pages 17-23

  Zhang, Bei ^a   Shanmugaraj, Balamurugan ^a   Daniell, Henry ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHLOROPLAST PROTEIN; RECOMBINANT PROTEIN;

BIOPHARMACEUTICAL; CHLOROPLAST; DRUG DELIVERY SYSTEM; EDIBLE PLANT; ENVIRONMENTAL TEMPERATURE; HUMAN; IMMUNOMODULATION; INFECTION; INFECTION PREVENTION; METABOLIC DISORDER; NONHUMAN; PHARMACOLOGICAL PARAMETERS; PLANT CELL; PROTEIN EXPRESSION; PROTEIN PROCESSING; REVIEW; ANIMAL; GENE EXPRESSION; GENETICS; METABOLISM; ORAL DRUG ADMINISTRATION; PLANT; PROCEDURES; PROTEIN ENGINEERING;

ADMINISTRATION, ORAL; ANIMALS; CHLOROPLASTS; GENE EXPRESSION; HUMANS; PLANTS; PROTEIN ENGINEERING; RECOMBINANT PROTEINS;

EID: 85013500966     PISSN: 13675931     EISSN: 18790402     Source Type: Journal    
DOI: 10.1016/j.cbpa.2017.02.007     Document Type: Review

References (54)

1. 1 Kwon, K.-C., Daniell, H., Low-cost oral delivery of protein drugs bioencapsulated in plant cells. Plant Biotechnol J 13 (2015), 1017–1022.
2. 2 Sabalza, M., Christou, P., Capell, T., Recombinant plant-derived pharmaceutical proteins: current technical and economic bottlenecks. Biotechnol Lett 36 (2014), 2367–2379.
3. 3 Daniell, H., Chan, H.-T., Pasoreck, E.K., Vaccination via chloroplast genetics: affordable protein drugs for the prevention and treatment of inherited or infectious human diseases. Annu Rev Genet 50 (2016), 595–618.
4. 4•• Su, J., Zhu, L., Sherman, A., Wang, X., Lin, S., Kamesh, A., Norikane, J.H., Streatfield, S.J., Herzog, R.W., Daniell, H., Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials 70 (2015), 84–93 This is the first commercial scale production of a biopharmaceutical protein in a cGMP facility in an edible plant cell, facilitating further clinical studies. This study also reported that biopharmaceutical proteins are stable at ambient temperature for several years maintaining their folding, assembly and functionality.
5. 5 Martens, E.C., Lowe, E.C., Chiang, H., Pudlo, N.A., Wu, M., McNulty, N.P., Abbott, D.W., Henrissat, B., Gilbert, H.J., Bolam, D.N., et al. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biol, 9, 2011, e1001221.
6. 6 Flint, H.J., Scott, K.P., Duncan, S.H., Louis, P., Forano, E., Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3 (2012), 289–306.
7. 7•• Xiao, Y., Kwon, K.-C., Hoffman, B.E., Kamesh, A., Jones, N.T., Herzog, R.W., Daniell, H., Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells. Biomaterials 80 (2016), 68–79 Several cell penetrating peptides suitable for protein drug delivery to different human cell types including non-immune and immune modulatory cells are investigated.
8. 8 Kwon, K.-C., Daniell, H., Oral delivery of protein drugs bioencapsulated in plant cells. Mol Ther 24 (2016), 1342–1350.
9. 9•• Kohli, N., Westerveld, D.R., Ayache, A.C., Verma, A., Shil, P., Prasad, T., Zhu, P., Chan, S.L., Li, Q., Daniell, H., Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers. Mol Ther 22 (2014), 535–546 First protein drug delivery across the blood–brain barrier, which is a major challenge in treatment of brain disorders.
10. 10•• Shil, P.K., Kwon, K.-C., Zhu, P., Verma, A., Daniell, H., Li, Q., Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis. Mol Ther 22 (2014), 2069–2082 First protein drug delivery across blood–retinal barrier, which is a major challenge in treatment of eye diseases.
11. 11•• Liu, Y., Kamesh, A.C., Xiao, Y., Sun, V., Hayes, M., Daniell, H., Koo, H., Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells. Biomaterials 105 (2016), 156–166 First example of topical drug delivery; biofilm causing dental caries was blocked from development using anti-microbial peptides (AMP); mature biofilms were disrupted my matrix degrading enzymes; AMPs also efficiently delivered protein drugs to different oral tissues.
12. 12 Rybicki, E.P., Plant-made vaccines for humans and animals. Plant Biotechnol J 8 (2010), 620–637.
13. 13 Chan, H.-T., Daniell, H., Plant-made oral vaccines against human infectious diseases—are we there yet?. Plant Biotechnol J 13 (2015), 1056–1070.
14. 14 Shahid, N., Daniell, H., Plant-based oral vaccines against zoonotic and non-zoonotic diseases. Plant Biotechnol J 14 (2016), 2079–2099.
15. 15 Pastores, G.M., Petakov, M., Giraldo, P., Rosenbaum, H., Szer, J., Deegan, P.B., Amato, D.J., Mengel, E., Tan, E.S., Chertkoff, R., et al. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase. Blood Cells Mol Dis 53 (2014), 253–260.
16. 16•• Boyhan, D., Daniell, H., Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide. Plant Biotechnol J 9 (2011), 585–598 First report of functional oral drug delivery using a suitable animal model and insulin expressed in edible plant chloroplasts. Both the CTB and proinsulin require disulfide bonds for functionality.
17. 17•• Ruhlman, T., Verma, D., Samson, N., Daniell, H., The role of heterologous chloroplast sequence elements in transgene integration and expression. Plant Physiol 152 (2010), 2088–2104 This study laid the foundation for expression of biopharmaceuticals in edible chloroplasts by developing species-specific chloroplast vectors and fully optimizing the lettuce transplastomic system.
18. 18 Waheed, M.T., Ismail, H., Gottschamel, J., Mirza, B., Lössl, A.G., Plastids: the Green Frontiers for vaccine production. Front Plant Sci, 6, 2015.
19. 19•• Chan, H.T., Xiao, Y., Weldon, W.C., Oberste, S.M., Chumakov, K., Daniell, H., Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes. Plant Biotechnol J 14 (2016), 2190–2200 This study conducted at the FDA, CDC and Daniell laboratories, funded by the Gates Foundation laid the foundation for developing booster vaccines against global infectious diseases; withdrawal of the oral polio vaccine 2 makes this an urgent unmet medical need for eradication of polio.
20. 20 Lakshmi, P.S., Verma, D., Yang, X., Lloyd, B., Daniell, H., Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro. PLoS One, 8, 2013, e54708.
21. 21•• Davoodi-Semiromi, A., Schreiber, M., Nallapali, S., Verma, D., Singh, N.D., Banks, R.K., Chakrabarti, D., Daniell, H., Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery. Plant Biotechnol J 8 (2010), 223–242 This study provides detailed mechanistic aspects of immunity and protection conferred by vaccine antigens orally delivered to suitable animal models.
22. 22• Koya, V., Moayeri, M., Leppla, S.H., Daniell, H., Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge. Infect Immun 73 (2005), 8266–8274 Animals were fully protected against anthrax toxin challenge when subcutaneouly immunized with anthrax protective antigen made in chloroplasts.
23. 23• Arlen, P.A., Singleton, M., Adamovicz, J.J., Ding, Y., Davoodi-Semiromi, A., Daniell, H., Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts. Infect Immun 76 (2008), 3640–3650 Animals were fully protected against plague aerosol challenge when orally immunized with plant cells expressing the vaccine antigen.
24. 24 Holaskova, E., Galuszka, P., Frebort, I., Oz, M.T., Antimicrobial peptide production and plant-based expression systems for medical and agricultural biotechnology. Biotechnol Adv 33 (2015), 1005–1023.
25. 25 Gupta, K., Kotian, A., Subramanian, H., Daniell, H., Ali, H., Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties. Oncotarget 6 (2015), 28573–28587.
26. 26•• DeGray, G., Rajasekaran, K., Smith, F., Sanford, J., Daniell, H., Expression of an antimicrobial peptide via the chloroplast genome to control phytopathogenic bacteria and fungi. Plant Physiol 127 (2001), 852–862 First report of an antimicrobial peptide made in plant chloroplasts.
27. 27• Lee, S.-B., Li, B., Jin, S., Daniell, H., Expression and characterization of antimicrobial peptides Retrocyclin-101 and Protegrin-1 in chloroplasts to control viral and bacterial infections. Plant Biotechnol J 9 (2011), 100–115 Both antimicrobial peptides require three disufide bonds for functionality; in addition, RC101 requires cyclization for antimicrobial activity.
28. 28 Cent. Dis. Control Prev. National diabetes statistics report: estimates of diabetes and its burden in the United States. Atlanta, GA: US Dep. Health Hum. Serv. 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf.
29. 29 Choi, J., Diao, H., Feng, Z.-C., Lau, A., Wang, R., Jevnikar, A.M., Ma, S., A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes. Plant Biotechnol J 12 (2014), 425–435.
30. 30• Kwon, K.-C., Nityanandam, R., New, J.S., Daniell, H., Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells. Plant Biotechnol J 11 (2013), 77–86 An ideal candidate for clinical translation because exendin is functional in a broad dose range and prevents hypoglycemia in 5000 excess dose.
31. 31 Carr, M.E., Tortella, B.J., Emerging and future therapies for hemophilia. J Blood Med 6 (2015), 245–255.
32. 32 DiMichele, D.M., Immune tolerance in haemophilia: the long journey to the fork in the road. Br J Haematol 159 (2012), 123–134.
33. 33 Kempton, C.L., Meeks, S.L., Toward optimal therapy for inhibitors in hemophilia. Blood 124 (2014), 3365–3372.
34. 34•• Verma, D., Moghimi, B., LoDuca, P.A., Singh, H.D., Hoffman, B.E., Herzog, R.W., Daniell, H., Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. Proc Natl Acad Sci USA 107 (2010), 7101–7106 This study laid the foundation for induction of oral tolerance in mice using biopharmaceuticals expressed in chloroplasts, in sharp contrast to previous reports on induction of immunity.
35. 35• Sherman, A., Su, J., Lin, S., Wang, X., Herzog, R.W., Daniell, H., Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells. Blood 124 (2014), 1659–1668 Reports an ideal candidate for clinical translation because antibody formation is a major challenge among hemophilia A patients; this is an unmet medical need because of lack of any other suitable treatments to address this concern.
36. 36•• Herzog, R.W., Nichols, T.C., Su, J., Zhang, B., Sherman, A., Merricks, E.P., Raymer, R., Perrin, G.Q., Hager, M., Wiinberg, B., et al. Oral Tolerance Induction in Hemophilia B Dogs Fed with Transplastomic Lettuce. Mol Ther 25 (2016), 512–522.
37. 37 Su, J., Sherman, A., Doerfler, P.A., Byrne, B.J., Herzog, R.W., Daniell, H., Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice. Plant Biotechnol J 13 (2015), 1023–1032.
38. 38 Xu, J., Dolan, M.C., Medrano, G., Cramer, C.L., Weathers, P.J., Green factory: plants as bioproduction platforms for recombinant proteins. Biotechnol Adv 30 (2012), 1171–1184.
39. 39 Lehtimäki, N., Koskela, M.M., Mulo, P., Posttranslational modifications of chloroplast proteins: an emerging field. Plant Physiol 168 (2015), 768–775.
40. 40 Cohen, P., The role of protein phosphorylation in human health and disease. Eur J Biochem 268 (2001), 5001–5010.
41. 41 Tan, C.S.H., Bodenmiller, B., Pasculescu, A., Jovanovic, M., Hengartner, M.O., Jørgensen, C., Bader, G.D., Aebersold, R., Pawson, T., Linding, R., Comparative analysis reveals conserved protein phosphorylation networks implicated in multiple diseases. Sci Signal, 2, 2009, ra39.
42. 42 Zhong, X., Wright, J.F., Biological insights into therapeutic protein modifications throughout trafficking and their biopharmaceutical applications. Int J Cell Biol, 2013, 2013, 19.
43. 43 Kalafatis, M., Identification and partial characterization of factor Va heavy chain kinase from human platelets. J Biol Chem 273 (1998), 8459–8466.
44. 44 Mori, Y., Hamuro, T., Nakashima, T., Hamamoto, T., Natsuka, S., Hase, S., Iwanaga, S., Biochemical characterization of plasma-derived tissue factor pathway inhibitor: post-translational modification of free, full-length form with particular reference to the sugar chain. J Thromb Haemost 7 (2009), 111–120.
45. 45 Zhou, Z., Mondal, M., Liao, G., Guo, Z., Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers. Org Biomol Chem 12 (2014), 3238–3245.
46. 46 Wittenberg, G., Danon, A., Disulfide bond formation in chloroplasts: formation of disulfide bonds in signaling chloroplast proteins. Plant Sci 175 (2008), 459–466.
47. 47• Daniell, H., Ruiz, G., Denes, B., Sandberg, L., Langridge, W., Optimization of codon composition and regulatory elements for expression of human insulin like growth factor-1 in transgenic chloroplasts and evaluation of structural identity and function. BMC Biotechnol 9 (2009), 33–48 Insulin like growth factor requires disufide bonds for functionality. Functional IGF-1 was produced in chloroplasts.
48. 48• Staub, J.M., Garcia, B., Graves, J., Hajdukiewicz, P.T.J., Hunter, P., Nehra, N., Paradkar, V., Schlittler, M., Carroll, J.A., Spatola, L., et al. High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat Biotechnol 18 (2000), 333–338 Somatotropin requires disufide bonds for functionality. Functional somatotropin was produced in chloroplasts.
49. 49• Arlen, P.A., Falconer, R., Cherukumilli, S., Cole, A., Cole, A.M., Oishi, K.K., Daniell, H., Field production and functional evaluation of chloroplast-derived interferon-α2b. Plant Biotechnol J 5 (2007), 511–525 Interferon α2b requires disufide bonds for functionality. Functional interferon α2b was produced in chloroplasts.
50. 50• Sanz-Barrio, R., Millán, A.F.-S., Corral-Martínez, P., Seguí-Simarro, J.M., Farran, I., Tobacco plastidial thioredoxins as modulators of recombinant protein production in transgenic chloroplasts. Plant Biotechnol J 9 (2011), 639–650 Human serum albumin requires 17 disufide bonds for functionality. Functional HSA was produced in chloroplasts.
51. 51 Meinnel, T., Giglione, C., Protein lipidation meets proteomics. Front Biosci 13 (2008), 6326–6340.
52. 52• Glenz, K., Bouchon, B., Stehle, T., Wallich, R., Simon, M.M., Warzecha, H., Production of a recombinant bacterial lipoprotein in higher plant chloroplasts. Nat Biotechnol 24 (2006), 76–77 The outer surface protein A requires lipidation to confer immunity. Functional vaccine antigen was produced in chloroplasts.
53. 53•• Kwon, K.-C., Chan, H.-T., León, I.R., Williams-Carrier, R., Barkan, A., Daniell, H., Codon optimization to enhance expression yields insights into chloroplast translation. Plant Physiol 172 (2016), 62–77 This is the first report of drug dose determination in planta. In addition, authors provide insight into chloroplast translation and address challenges in expression of large human or viral genes in chloroplasts.
54. 54 Day, A., Goldschmidt-Clermont, M., The chloroplast transformation toolbox: selectable markers and marker removal. Plant Biotechnol J 9 (2011), 540–553.