From neanderthal to nanobiotech: From plant potions to pharming with plant factories

Methods in Molecular Biology

Volumn 483, Issue , 2009, Pages 1-23

  Sourrouille, Christophe ^a   Marshall, Brian ^b   Liénard, David ^a   Faye, Loïc ^a  

^a UNIVERSITÉ DE ROUEN   (France)

^b MolecularFarmingcom   (Ireland)

Author keywords

Glycosylation; Molecular farming; Plant made pharmaceutical; Recombinant protein; Therapeutic protein; Transgenic plant

Indexed keywords

ANIMALIA; BACTERIA (MICROORGANISMS); MAMMALIA;

DRUG; RECOMBINANT PROTEIN;

BIOSYNTHESIS; BIOTECHNOLOGY; METABOLISM; NANOTECHNOLOGY; REVIEW; TRANSGENIC PLANT;

BIOTECHNOLOGY; NANOTECHNOLOGY; PHARMACEUTICAL PREPARATIONS; PLANTS, GENETICALLY MODIFIED; RECOMBINANT PROTEINS;

EID: 60549108896     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-59745-407-0_1     Document Type: Review

References (93)

1. Walsh, G., and Jefferis, R. (2006) Posttranslational modifications in the context of therapeutic proteins. Nat. Biotechnol. 24, 1241-1252.
2. Gomord, V., and Faye, L. (2004) Posttranslational modification of therapeutic proteins in plants. Curr. Opin. Plant Biol. 7, 171-181.
3. Twyman, R.M., Stoger, E., Schillberg, S., Christou, P., and Fischer, R. (2003) Molecular farming in plants: host systems and expression technology. Trends Biotechnol. 21, 570-578.
4. Gomord, V., Sourrouille, C., Fitchette, A.-C., Bardor, M., Pagnt, S., Lerouge, P., and Faye, L. (2004) Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge. Plant Biotechnol. J. 2, 83-100.
5. Hiatt, A., Cafferkey, R., and Bowdish, K. (1989) Production of antibodies in transgenic plants. Nature 342, 76-78.
6. Ma, J.K., Hiatt, A., Hein, M., Vine, N.D., Wang, F., Stabila, P., van Dolleweerd, C., Mostov, K., and Lehner, T. (1995) Generation and assembly of secretory antibodies in plants. Science 268, 716-719.
7. Khoudi, H., Laberge, S., Ferullo, J.M., Bazin, R., Darveau, A., Castonguay, Y., Allard, G., Lemieux, R., and Vezina, L.P. (1999) Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol. Bioeng. 64, 135-143.
8. Austin, S., Bingham, E.T., Koegel, R.G., Mathews, D.E., Shahan, M.N., Straub, R.J., and Burgess, R.R. (1994) An overview of a feasibility study for the production of industrial enzymes in transgenic alfalfa. Ann. N. Y. Acad. Sci. 721, 234-244.
9. Gomord, V., Chamberlain, P., Jefferis, R., and Faye, L. (2005) Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol. 23, 559-565.
10. Cabanes-Macheteau, M., Fitchette-Laine, A.C., Loutelier-Bourhis, C., Lange, C., Vine, N.D., Ma, J.K., Lerouge, P., and Faye, L. (1999) N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology 9, 365-372.
11. Bakker, H., Bardor, M., Molthoff, J.W., Gomord, V., Elbers, I., Stevens, L.H., Jordi, W., Lommen, A., Faye, L., Lerouge, P., and Bosch, D. (2001) Galactose-extended glycans of antibodies produced by transgenic plants. Proc. Natl. Acad. Sci. U. S. A. 98, 2899-2904.
12. Bouquin, T., Thomsen, M., Nielsen, L.K., Green, T.H., Mundy, J., and Hanefeld Dziegiel, M. (2002) Human anti-rhesus D IgG1 antibody produced in transgenic plants. Transgenic Res. 11, 115-122.
13. Streatfield, S.J. (2007) Approaches to achieve high-level heterologous protein production in plants. Plant Biotechnol. J. 5, 2-15.
14. Perlak, F.J., Fuchs, R.L., Dean, D.A., McPherson, S.L., and Fischhoff, D.A. (1991) Modification of the coding sequence enhances plant expression of insect control protein genes. Proc. Natl. Acad. Sci. U. S. A. 88, 3324-3328.
15. Jensen, L.G., Olsen, O., Kops, O., Wolf, N., Thomsen, K.K., and von Wettstein, D. (1996) Transgenic barley expressing a protein-engineered, thermostable (1,3-1,4)-beta-glucanase during germination. Proc. Natl. Acad. Sci. U. S. A. 93, 3487-3491.
16. Batard, Y., Hehn, A., Nedelkina, S., Schalk, M., Pallett, K., Schaller, H., and Werck-Reichhart, D. (2000) Increasing expression of P450 and P450-reductase proteins from monocots in heterologous systems. Arch. Biochem. Biophys. 379, 161-169.
17. Hamada, A., Yamaguchi, K.-I., Ohnishi, N., Harada, M., Nikumaru, S., and Honda, H. (2005) High-level production of yeast (Schwanniomyces occidentalis) phytase in transgenic rice plants by a combination of signal sequence and codon modification of the phytase gene. Plant Biotechnol. J. 3, 43-55.
18. Hamilton, A.J., and Baulcombe, D.C. (1999). A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950-952.
19. Voinnet, O. (2005) Induction and suppression of RNA silencing: insights from viral infections. Nat. Rev. Genet. 6, 206-220.
20. Scholthof, H.B., Scholthof, K.B., and Jackson, A.O. (1995) Identification of tomato bushy stunt virus host-specific symptom determinants by expression of individual genes from a potato virus X vector. Plant Cell 7, 1157-1172.
21. Voinnet, O., Rivas, S., Mestre, P., and Baulcombe, D. (2003) An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus. Plant J. 33, 949-956.
22. Voinnet, O., Pinto, Y.M., and Baulcombe, D.C. (1999) Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants. Proc. Natl. Acad. Sci. U. S. A. 96, 14147-14152.
23. Goldstein, D.A., and Thomas, J.A. (2004) Biopharmaceuticals derived from genetically modified plants. Q. J. Med. 97, 705-716.
24. Hellwig, S., Drossard, J., Twyman, R.M., and Fischer, R. (2004) Plant cell cultures for the production of recombinant proteins. Nat. Biotechnol. 22, 1415-1422.
25. Masumura, T., Morita, S., Miki, Y., Kurita, A., Morita, S., Shirono, H., Koga, J., and Tanaka , K. (2006) Production of biologically active human interferon-alpha in transgenic rice. Plant Biotechnol. J. 23, 91-97.
26. Shirono, H., Morita, S., Miki, Y., Kurita, A., Morita, S., Koga, J., Tanaka, K., and Masumura, T. (2006) Highly efficient production of human interferon-alpha by transgenic cultured rice cells. Plant Biotechnol. J. 23, 283-289.
27. Vancanneyt, G., Dubald, M., Schröder, W., Peters, J., and Botterman, J. (2008) A case study for plant-made pharmaceuticals comparing different plant expression and production systems. This issue.
28. Goldstein, D.A., and Thomas, J.A. (2004) Biopharmaceuticals derived from genetically modified plants. Q. J. Med. 97, 705-716.
29. Streatfield, S.J. (2007) Approaches to achieve high-level heterologous protein production in plants. Plant Biotechnol. J. 5, 2-15.
30. Lienard, D., Tran Dinh, O., van Oort, E., Van Overtvelt, L., Bonneau, C., Wambre, E., Bardor, M., Cosette, P., Didier-Laurent, A., Dorlhac de Borne, F., Delon, R., van Ree, R., Moingeon, P., Faye, L., and Gomord, V. (2007) Suspension-cultured BY-2 tobacco cells produce and mature immunologically active house dust mite allergens, Chapter 12 in this book. Plant Biotechnol. J. 5, 93-108.
31. Conrad, U., and Fiedler, U. (1998) Compartment-specific accumulation of recombinant immunoglobulins in plant cells: an essential tool for antibody production and immunomodulation of physiological functions and pathogen activity. Plant Mol. Biol. 38, 101-109.
32. Wandelt, C.I., Khan, M.R., Craig, S., Schroeder, H.E., Spencer, D., and Higgins, T.J. (1992) Vicilin with carboxy- terminal KDEL is retained in the endoplasmic reticulum and accumulates to high levels in the leaves of transgenic plants. Plant J. 2, 181-192.
33. Vitale, A., and Pedrazzini, E. (2005) Recombinant pharmaceuticals from plants: the plant endomembrane system as bioreactor. Mol. Interv. 5, 216-225.
34. Arcalis, E., Marcel, S., Altmann, F., Kolarich, D., Drakakaki, G., Fischer, R., Christou, P., and Stoger, E. (2004) Unexpected deposition patterns of recombinant proteins in post-endoplasmic reticulum compartments of wheat endosperm. Plant Physiol. 136, 3457-3466.
35. Rademacher, T., Arcalis, E., and Stoger, E. (2008) Production and localization of recombinant pharmaceuticals in transgenic seeds. Chapter 5 in this book
36. Torrent, M., Llop, I., and Ludevid, M.D. (2008) Protein body induction: a new tool to produce and recover recombinant proteins in plants. This issue
37. van Rooijen, G.J., and Moloney, M.M. (1995) Structural requirements of oleosin domains for subcellular targeting to the oil body, Chapter 11 in this book. Plant Physiol. 109, 1353-1361.
38. Nykiforuk, C.L., Boothe, J.G., Murray, E.W., Keon, R.G., Goren, H.J., Markley, N.A., and Moloney, M.M. (2006) Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds. Plant Biotechnol. J. 4, 77-86.
39. Daniell, H., and Dhingra, A. (2002) Multigene engineering: dawn of an exciting new era in biotechnology. Curr. Opin. Biotechnol. 13, 136-141.
40. De Cosa, B., Moar, W., Lee, S.B., Miller, M., and Daniell, H. (2001) Overexpression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals. Nat. Biotechnol. 19, 71-74.
41. Singh, N.D., Ding, Y., and Daniell, H. (2008) Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for expression, purification or oral delivery and functional evaluation. This issue
42. Staub, J.M., Garcia, B., Graves, J., Hajdukiewicz, P.T., Hunter, P., Nehra, N., Paradkar, V., Schlittler, M., Carroll, J.A., Spatola, L., Ward, D., Ye, G., and Russell, D.A. (2000) High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat. Biotechnol. 18, 333-338.
43. Jobling, S.A., Jarman, C., Teh, M.M., Holmberg, N., Blake, C., and Verhoeyen, M.E. (2003) Immunomodulation of enzyme function in plants by single- domain antibody fragments. Nat. Biotechnol. 21, 77-80.
44. Daniell, H., Streatfield, S.J., and Wycoff, K. (2001) Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci. 6, 219-226.
45. Mayfield, S.P., Franklin, S.E., and Lerner, R.A. (2003) Expression and assembly of a fully active antibody in algae. Proc. Natl. Acad. Sci. U. S. A. 100, 438-442.
46. Faye, L., and Daniell, H. (2006) Novel pathway for glycoprotein import into chloroplasts. Plant Biotechnol. J. 4, 275-279.
47. Michaud, D., Vrain, T., Gomord, V., and Faye, L. (1998) Stability of recombinant proteins in plants. In Methods in biotechnology. Recombinant proteins from plants - production and isolation of clinically useful compounds, P. AJR, ed. (Totowa (NJ): Humana Press), pp. 177-188.
48. Michaud, D. (1998) Gel electrophoresis of proteolytic enzymes. Anal. Chim. Acta 372, 173-185.
49. Schouten, A., Roosien, J., van Engelen, F.A., de Jong, G.A., Borst-Vrenssen, A.W., Zilverentant, J.F., Bosch, D., Stiekema, W.J., Gommers, F.J., Schots, A., and Bakker, J. (1996) The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Mol. Biol. 30, 781-793.
50. Pagny, S., Cabanes-Macheteau, M., Gillikin, J.W., Leborgne-Castel, N., Lerouge, P., Boston, R.S., Faye, L., and Gomord, V. (2000) Protein recycling from the Golgi apparatus to the endoplasmic reticulum in plants and its minor contribution to calreticulin retention. Plant Cell 12, 739-756.
51. Wong, E.Y., Hironaka, C.M., and Fischhoff, D.A. (1992) Arabidopsis thaliana small subunit leader and transit peptide enhance the expression of Bacillus thuringiensis proteins in transgenic plants. Plant Mol. Biol. 20, 81-93.
52. Benchabane, M., Rivard, D., Girard, C., and Michaud, D. (XXXX) Companion protease inhibitors to protect recombinant proteins in transgenic plant extracts. This issue
53. Rivard, D., Anguenot, R., Brunelle, F., Le, V.Q., Vézina, L.P., Trépanier, S., Michaud, D. (2006) An in-built proteinase inhibitor system for the protection of recombinant proteins recovered from transgenic plants. Plant Biotechnol. J. 4, 359-368.
54. Merle, C., Perret, S., Lacour, T., Jonval, V., Hudaverdian, S., Garrone, R., Ruggiero, F., and Theisen, M. (2002) Hydroxylated human homotrimeric collagen I in Agrobacterium tumefaciens-mediated transient expression and in transgenic tobacco plant. FEBS Lett. 515, 114-118.
55. Saint-Jore-Dupas, C., Faye, L., and Gomord, V. (2007) From planta to pharma with glycosylation in the toolbox. Trends Biotechnol. 25, 317-323.
56. Aalberse, R.C., Koshte, V., and Clemens, J.G. (1981) Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and Hymenoptera venom. J. Allergy Clin. Immunol. 68, 356-364.
57. Faye, L., and Chrispeels, M.J. (1985) Characterization of N-linked oligosaccharides by affinoblotting with concanavalin A- peroxidase and treatment of the blots with glycosidases. Anal. Biochem. 149, 218-224.
58. Aalberse, R.C., Koshte, V., and Clemens, J.G. (1981) Cross-reactions between vegetable foods, pollen and bee venom due to IgE antibodies to a ubiquitous carbohydrate determinant. Int. Arch. Allergy Appl. Immunol. 66, 259-260.
59. Bardor, M., Faveeuw, C., Fitchette, A.C., Gilbert, D., Galas, L., Trottein, F., Faye, L., and Lerouge, P. (2003) Immunoreactivity in mammals of two typical plant glycoepitopes, core alpha(1,3)-fucose and core xylose. Glycobiology 13, 427-434.
60. Jin, C., Bencurova, M., Borth, N., Ferko, B., Jensen-Jarolim, E., Altmann, F., and Hantusch, B. (2006) Immunoglobulin G specifically binding plant N-glycans with high affinity could be generated in rabbits but not in mice. Glycobiology 16, 349-357.
61. Nuttall, J., Ma, J.K., and Frigerio, L. (2005) A functional antibody lacking N-linked glycans is efficiently folded, assembled and secreted by tobacco mesophyll protoplasts. Plant Biotechnol. J. 3, 497-504.
62. Sriraman, R., Bardor, M., Sack, M., Vaquero, C., Faye, L., Fischer, R., Finnern, R., and Lerouge, P. (2004) Recombinant anti-hCG antibodies retained in the endoplasmic reticulum of transformed plants lack core-xylose and core-alpha(1,3)-fucose residues. Plant Biotechnol. J. 2, 279-287.
63. Petruccelli, S., Otegui, M.S., Lareu, F., Tran Dinh, O., Fitchette, A.-C., Circosta, A., Rumbo, M., Bardor, M., Carcamo, R., Gomord, V., and Beachy, R.N. (2006) A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds. Plant Biotechnol. J. 4, 511-527.
64. Strasser, R., Altmann, F., Mach, L., Glossl, J., and Steinkellner, H. (2004) Generation of Arabidopsis thaliana plants with complex N-glycans lacking beta1,2-linked xylose and core alpha1,3-linked fucose. FEBS Lett. 561, 132-136.
65. Koprivova, A., Stemmer, C., Altmann, F., Hoffmann, A., Kopriva, S., Gorr, G., Reski, R., and Decker, E.L. (2004) Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol. J. 2, 517-523.
66. Cox, K.M., Sterling, J.D., Regan, J.T., Gasdaska, J.R., Frantz, K.K., Peele, C.G., Black, A., Passmore, D., Moldovan-Loomis, C., Srinivasan, M., Cuison, S., Cardarelli, P.M., and Dickey, L.F. (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat. Biotechnol. 24, 1591-1597.
67. Sourrouille, C. (2005) Inactivation de l'alpha (1,3)- fucosyltransférase et de la beta (1,2)-xylosyltransferase, en vue de la production de protéines recombinantes d'intérêt thérapeutique chez la luzerne (Université de Rouen), pp. 164.
68. Schahs, M., Strasser, R., Stadlmann, J., Kunert, R., Rademacher, T., and Steinkellner, H. (2007) Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol. J. 5, 657-663.
69. Schuster, M., Jost, W., Mudde, G.C., Wiederkum, S., Schwager, C., Janzek, E., Altmann, F., Stadlmann, J., Stemmer, C., and Gorr, G. (2007) In vivo glyco-engineered antibody with improved lytic potential produced by an innovative non-mammalian expression system. Biotechnol. J. 2, 700-708.
70. Misaki, R., Kimura, Y., Palacpac, N.Q., Yoshida, S., Fujiyama, K., and Seki, T. (2003) Plant cultured cells expressing human beta1,4- galactosyltransferase secrete glycoproteins with galactose-extended N-linked glycans. Glycobiology 13, 199-205.
71. Fujiyama, K., Palacpac, N.Q., Sakai, H., Kimura, Y., Shinmyo, A., Yoshida, T., and Seki, T. (2001) In vivo conversion of a glycan to human compatible type by transformed tobacco cells. Biochem. Biophys. Res. Commun. 289, 553-557.
72. Saint-Jore-Dupas, C., Nebenfuhr, A., Boulaflous, A., Follet-Gueye, M.L., Plasson, C., Hawes, C., Driouich, A., Faye, L., and Gomord, V. (2006) Plant N-glycan processing enzymes employ different targeting mechanisms for their spatial arrangement along the secretory pathway. Plant Cell 18, 3182-3200.
73. Bakker, H., Rouwendal, G.J., Karnoup, A.S., Florack, D.E., Stoopen, G.M., Helsper, J.P., van Ree, R., van Die, I., and Bosch, D. (2006) An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proc. Natl. Acad. Sci. U. S. A. 103, 7577-7582.
74. Seveno, M., Bardor, M., Paccalet, T., Gomord, V., Lerouge, P., and Faye, L. (2004) Glycoprotein sialylation in plants ? Nat. Biotechnol. 22, 1351-1352; 1352-1353.
75. Zeleny, R., Kolarich, D., Strasser, R., and Altmann, F. (2006) Sialic acid concentrations in plants are in the range of inadvertent contamination. Planta 224, 222-227.
76. Jarvis, D.L. (2003) Developing baculovirus-insect cell expression systems for humanized recombinant glycoprotein production. Virology 310, 1-7.
77. Wee, E.G., Sherrier, D.J., Prime, T.A., and Dupree, P. (1998) Targeting of active sialyltransferase to the plant Golgi apparatus. Plant Cell 10, 1759-1768.
78. Misaki, R., Fujiyama, K., and Seki, T. (2006) ExpressionofhumanCMP-N- acetylneuraminic acid synthetase and CMP-sialic acid transporter in tobacco suspension-cultured cell. Biochem. Biophys. Res. Commun. 339, 1184-1189.
79. Paccalet, T., Bardor, M., Rihouey, C., Delmas, F., Chevalier, C., D'Aoust, M.-A., Faye, L., Vezina, L.P., Gomord, V., and Lerouge, P. (2007) Engineering of a sialic acid synthesis pathway in transgenic plants by expression of bacterial Neu5Ac-synthesizing enzymes. Plant Biotechnol. J. 5, 16-25.
80. Jefferis, R. (XXXX) Glycosylation of antibody therapeutics: optimisation for purpose. This issue
81. Schaefer, D., Zryd, J.P., Knight, C.D., and Cove, D.J. (1991) Stable transformation of the moss Physcomitrella patens. Mol. Gen. Genet. 226, 418-424.
82. Schaefer, D.G., and Zryd, J.P. (1997) Efficient gene targeting in the moss Physcomitrella patens. Plant J. 11, 1195-1206.
83. Lienard, D., and Nogué, F. (XXXX) Physcomitrella patens: a non-vascular plant for recombinant protein production. This issue.
84. Baur, A., Reski, R., and Gorr, G. (2005) Enhanced recovery of a secreted recombinant human growth factor using stabilizing additives and by co-expression of human serum albumin in the moss Physcomitrella patens. Plant Biotechnol. J. 3, 331-340.
85. Schaefer, D.G., Bisztray, G., and Zrÿd, J.-P. (1994) Genetic transformation of the moss Physcomitrella patens. In Plant protoplasts and genetic engineering, V, Y.P.S. Bajaj, ed. (Berlin, Heidelberg, New York: Springer Verlag), pp. 349-364.
86. Vietor, R., Loutelier, B.C., Fitchette, A., Margerie, P., Gonneau, M., Faye, L., and Lerouge, P. (2003) Protein N-glycosylation is similar in the moss Physcomitrella patens and in higher plants. Planta 218, 269-275.
87. Franklin, S.E., and Mayfield, S.P. (2004) Prospects for molecular farming in the green alga Chlamydomonas. Curr. Opin. Plant Biol. 7, 159-165.
88. Leon-Banares, R., Gonzalez-Ballester, D., Galvan, A., and Fernandez, E. (2004) Transgenic microalgae as green cell-factories. Trends Biotechnol. 22, 45-52.
89. Boynton, J.E., Gillham, N.W., Harris, E.H., Hosler, J.P., Johnson, A.M., Jones, A.R., Randolph-Anderson, B.L., Robertson, D., Klein, T.M., Shark, K.B., et al. (1988) Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. Science 240, 1534-1538.
90. Mayfield, S.P., and Franklin, S.E. (2005) Expression of human antibodies in eukaryotic micro-algae. Vaccine 23, 1828-1832.
91. Gasdaska, J.R., Spencer, D., and Dickey, L.F. (2003) Advantages of therapeutic protein production in the aquatic plant Lemna. Bioprocessing J. 3, 50-56.
92. Shaaltiel, Y., Bartfeld, D., Hashmueli, S., Baum, G., Brill-Almon, E., Galili, G., Dym, O., Boldin-Adamsky, S.A., Silman, I., Sussman, J.L., Futerman, A.H., and Aviezer, D. (2007) Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. Plant Biotechnol. J. 5, 579-590.
93. Elbers, I.J., Stoopen, G.M., Bakker, H., Stevens, L.H., Bardor, M., Molthoff, J.W., Jordi, W.J., Bosch, D., and Lommen, A. (2001) Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves. Plant Physiol. 126, 1314-1322.