Current advances in the algae-made biopharmaceuticals field

References

• Finckh A, Neto D, Iannone F, et al. The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries. RMD Open. 2015;1(1):e000040.
   PubMed Web of Science ®Google Scholar
• Rader RA. (Re) defining biopharmaceutical. Nat Biotechnol. 2008;26(7):743–751.
   PubMed Web of Science ®Google Scholar
• Schellekens H. How similar ‘biosimilars’ need to be? Nat Biotechnol. 2004;22(11):1357–1359.
   PubMed Web of Science ®Google Scholar
• Dhara VG, Naik HM, Modjeska N, et al. Recombinant antibody production in CHO and NS0 Cells: differences and similarities. BioDrugs. 2018;32(6):571–584.
   PubMed Web of Science ®Google Scholar
• Kis Z, Shattuck R, Shah N, et al. Emerging technologies for low‐cost, rapid vaccine manufacture. Biotechnol J. 2019;14(1):1800376.
   PubMed Web of Science ®Google Scholar
• Ritacco FV, Wu Y, Khetan A. Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: history, key components, and optimization strategies. Biotechnol Prog. 2018;34(6):1407–1426.
   PubMed Web of Science ®Google Scholar
• Sanchez-Garcia L, Martin L, Mangues R, et al. Recombinant pharmaceuticals from microbial cells: a 2015 update. Microb Cell Fact. 2016;15:33.
   PubMed Web of Science ®Google Scholar
• Sivakumar G, editor. New insights into cell culture technology. Rijeka, Croatia: InTech; 2017. p. 43–97.
   Google Scholar
• Yan N, Fan C, Chen Y, et al. The potential for microalgae as bioreactors to produce pharmaceuticals. Int J Mol Sci. 2016;17(6):962.
   Web of Science ®Google Scholar
• Mayfield SP, Franklin SE, Lerner RA. Expression and assembly of a fully active antibody in algae. Proc Natl Acad Sci USA. 2003;100(2):438–442.
   PubMed Web of Science ®Google Scholar
• Gimpel JA, Henríquez V, Mayfield SP. In metabolic engineering of eukaryotic microalgae: potential and challenges come with great diversity. Front Microbiol. 2015a;6:1376.
   PubMed Web of Science ®Google Scholar
• Alam A, Jiang L, Kittleson GA, et al. Technoeconomic modeling of plant-based Griffithsin manufacturing. Front Bioeng Biotechnol. 2018;6:102.
   PubMed Web of Science ®Google Scholar
• Twyman RM, Stoger E, Schillberg S, et al. Molecular farming in plants: host systems and expression technology. Trends Biotechnol. 2003;21(12):570–578.
   PubMed Web of Science ®Google Scholar
• Draaisma RB, Wijffels RH, Slegers PM, et al. Food commodities from microalgae. Curr Opin Biotechnol. 2013;24(2):169–177.
   PubMed Web of Science ®Google Scholar
• Rasala BA, Mayfield SP. Photosynthetic biomanufacturing in green algae; production of recombinant proteins for industrial, nutritional, and medical uses. Photosynth Res. 2015;123:227–239.
   PubMed Web of Science ®Google Scholar
• Erdene-Ochir E, Shin BK, Kwon B, et al. Identification and characterisation of the novel endogenous promoter HASP1 and its signal peptide from Phaeodactylum tricornutum. Sci Rep. 2019 July 9;9(1):9941.
   PubMedGoogle Scholar
• Zhang Z, He P, Zhou Y, et al. Anti-HBV effect of interferon-thymosin α1 recombinant proteins in transgenic Dunaliella salina in vitro and in vivo. Exp Ther Med. 2018 Aug;16(2):517–522.
   PubMed Web of Science ®Google Scholar
• Niu YF, Zhang MH, Xie WH, et al. A new inducible expression system in a transformed green alga, Chlorella vulgaris. Genet Mol Res. 2011 Oct 21;10(4):3427–3434.
   PubMed Web of Science ®Google Scholar
• Ramos-Vega A, Rosales-Mendoza S, Bañuelos-Hernández B, et al. Prospects on the use of Schizochytrium sp. to develop oral vaccines. Front Microbiol. 2018 Oct;25(9):2506.
   Google Scholar
• Schroda M. The Chlamydomonas genome reveals its secrets: chaperone genes and the potential roles of their gene products in the chloroplast. Photosynth Res. 2004;82(3):221–240.
   PubMed Web of Science ®Google Scholar
• Breiman A, Fawcett TW, Ghirardi ML, et al. Plant organelles contain distinct peptidylprolyl cis, trans-isomerases. J Biol Chem. 1992;267(30):21293–21296.
   PubMed Web of Science ®Google Scholar
• Anyaogu DC, Mortensen UH. Manipulating the glycosylation pathway in bacterial and lower eukaryotes for production of therapeutic proteins. Curr Opin Biotechnol. 2015;36:122–128.
   PubMed Web of Science ®Google Scholar
• Mócsai R, Figl R, Troschl C, et al. N-glycans of the microalga Chlorella vulgaris are of the oligomannosidic type but highly methylated. Sci Rep. 2019 Jan 23;9(1):331.
   PubMedGoogle Scholar
• Tran M, Zhou B, Pettersson PL, et al. Synthesis and assembly of a full-length human monoclonal antibody in algal chloroplasts. Biotechnol Bioeng. 2009;104(4):663–673.
   PubMed Web of Science ®Google Scholar
• Ortega-Berlanga B, Bañuelos-Hernández B, Rosales-Mendoza S. Efficient expression of an Alzheimer’s disease vaccine candidate in the microalga Schizochytrium sp. using the Algevir system. Mol Biotechnol. 2018;60(5):362–368.
   PubMed Web of Science ®Google Scholar
• Kwon KC, Lamb A, Fox D, et al. An evaluation of microalgae as a recombinant protein oral delivery platform for fish using green fluorescent protein (GFP). Fish Shellfish Immunol. 2019 Apr;87:414–420. Epub 2019 Jan 28.
   PubMed Web of Science ®Google Scholar
• Chen Q. Expression and Purification of Pharmaceutical Proteins in Plants. Biol Eng. 2008;1(4):291–321.
   Google Scholar
• McNulty MJ, Gleba Y, Tusé D, et al. Techno‐economic analysis of a plant‐based platform for manufacturing antimicrobial proteins for food safety. Biotechnol Prog. 2020;36(1):1-15:e2896.
   PubMed Web of Science ®Google Scholar
• Vazquez-Villegas P, Torres-Acosta MA, Garcia-Echauri SA, et al. Genetic manipulation of microalgae for the production of bioproducts. Front Biosci (Elite Ed). 2018;10:254–275.
   PubMedGoogle Scholar
• Rosales-Mendoza S. Future directions for the development of Chlamydomonas-based vaccines. Expert Rev Vaccines. 2013;12(9):1011–1019.
   PubMed Web of Science ®Google Scholar
• Lauersen KJ, Huber I, Wichmann J, et al. Investigating the dynamics of recombinant protein secretion from a microalgal host. J Biotechnol. 2015;215:62–71.
   PubMed Web of Science ®Google Scholar
• Hempel F, Maier UG. An engineered diatom acting like a plasma cell secreting human IgG antibodies with high efficiency. Microb Cell Fact. 2012;11:126.
   PubMed Web of Science ®Google Scholar
• Rasala BA, Lee PA, Shen Z, et al. Robust expression and secretion of Xylanase1 in Chlamydomonas reinhardtii by fusion to a selection gene and processing with the FMDV 2A peptide. PLoS One. 2012;7:e43349.
   PubMed Web of Science ®Google Scholar
• Lauersen KJ, Vanderveer TL, Berger H, et al. Ice recrystallization inhibition mediated by a nuclear-expressed and -secreted recombinant ice-binding protein in the microalga Chlamydomonas reinhardtii. Appl Microbiol Biotechnol. 2013;97(22):9763–9772.
   PubMed Web of Science ®Google Scholar
• Bayne AC, Boltz D, Owen C, et al., Vaccination against influenza with recombinant hemagglutinin expressed by Schizochytrium sp. confers protective immunity. PLoS One. 8(4): e61790. 2013.
   PubMed Web of Science ®Google Scholar
• Dong B, Hu H, Li Z, et al. A novel bicistronic expression system composed of the intraflagellar transport protein gene ift25 and FMDV 2A sequence directs robust nuclear gene expression in Chlamydomonas reinhardtii. Appl Microbiol Biotechnol. 2017;101:4227–4245.
   PubMed Web of Science ®Google Scholar
• Shao N, Bock R. A codon-optimized luciferase from Gaussia princeps facilitates the in vivo monitoring of gene expression in the model alga Chlamydomonas reinhardtii. Curr Genet. 2008;53:381–388.
   PubMed Web of Science ®Google Scholar
• Molino JVD, de Carvalho JCM, Mayfield SP. Comparison of secretory signal peptides for heterologous protein expression in microalgae: expanding the secretion portfolio for Chlamydomonas reinhardtii. PLoS One. 2018 Feb 6;13(2):e0192433.
   Web of Science ®Google Scholar
• Kilian O 1, Benemann CS, Niyogi KK, et al. High-efficiency homologous recombination in the oil-producing alga Nannochloropsis sp. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21265–21269. Epub 2011 Nov 28.
   PubMed Web of Science ®Google Scholar
• Levitan A, Trebitsh T, Kiss V, et al. Dual targeting of the protein disulfide isomerase RB60 to the chloroplast and the endoplasmic reticulum. Proc Natl Acad Sci USA. 2005;102(17):6225–6230.
   PubMed Web of Science ®Google Scholar
• Tran M, Henry RE, Siefker D, et al. Production of anti-cancer immunotoxins in algae: ribosome inactivating proteins as fusion partners. Biotechnol Bioeng. 2013b;110(11):2826–2835.
   PubMed Web of Science ®Google Scholar
• Doron L, Segal N, Shapira M. Transgene expression in microalgae-from tools to applications. Front Plant Sci. 2016;7:505.
   PubMed Web of Science ®Google Scholar
• Bock R, Warzecha H. Solar-powered factories for new vaccines and antibiotics. Trends Biotechnol. 2010;28(5):246–252.
   PubMed Web of Science ®Google Scholar
• Murakami M, Kiuchi T, Nishihara M, et al. Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity. Sci Adv. 2016 Jan 15;2(1):1500678.
   Web of Science ®Google Scholar
• Wada R, Matsui M, Kawasaki N. Influence of N-glycosylation on effector functions and thermal stability of glycoengineered IgG1 monoclonal antibody with homogeneous glycoforms. mAbs. 2019;11(2):350–372.
   PubMed Web of Science ®Google Scholar
• Gimpel JA, Hyun JS, Schoepp NG, et al., Production of recombinant proteins in microalgae at pilot greenhouse scale. Biotechnol Bioeng. 112(2): 339–345. 2015b.
   PubMed Web of Science ®Google Scholar
• Dyo YM, Purton S. The algal chloroplast as a synthetic biology platform for production of therapeutic proteins. Microbiology. 2018;164(2):113–121.
   PubMed Web of Science ®Google Scholar
• Rasala BA, Chao SS, Pier M, et al. Enhanced genetic tools for engineering multigene traits into green algae. PLoS One. 2014;9(4):e94028.
   PubMed Web of Science ®Google Scholar
• Barahimipour R, Neupert J, Bock R. Efficient expression of nuclear transgenes in the green alga Chlamydomonas: synthesis of an HIV antigen and development of a new selectable marker. Plant Mol Biol. 2016;90:403–418.
   PubMed Web of Science ®Google Scholar
• Fuhrmann M, Oertel W, Hegemann P. A synthetic gene coding for the green fluorescent protein (GFP) is a versatile reporter in Chlamydomonas reinhardtii. Plant J. 1999;19:353–361.
   PubMed Web of Science ®Google Scholar
• Lee S, Lee YJ, Choi S, et al. Development of an alcohol-inducible gene expression system for recombinant protein expression in Chlamydomonas reinhardtii. Appl Phycol. 2018;30(4):2297–2304.
   Web of Science ®Google Scholar
• Cerutti H, Casas-Mollano JA. On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet. 2006;50(2):81–99.
   PubMed Web of Science ®Google Scholar
• Kurniasih SD, Yamasaki T, Kong F, et al. UV-mediated Chlamydomonas mutants with enhanced nuclear transgene expression by disruption of DNA methylation-dependent and independent silencing systems. Plant Mol Biol. 2016;92(6):629–641.
   PubMed Web of Science ®Google Scholar
• Neupert J, Karcher D, Bock R. Generation of Chlamydomonas strains that efficiently express nuclear transgenes. Plant J. 2009;57(6):1140–1150.
   PubMed Web of Science ®Google Scholar
• Baier T, Wichmann J, Kruse O, et al. Intron-containing algal transgenes mediate efficient recombinant gene expression in the green microalga Chlamydomonas reinhardtii. Nucleic Acids Res. 2018b;46:136909–136919.
   Web of Science ®Google Scholar
• Ramos‐Martinez EM, Fimognari L, Sakuragi Y. High‐yield secretion of recombinant proteins from the microalga Chlamydomonas reinhardtii. Plant Biotech J. 2017;15(9):1214–1224.
   PubMed Web of Science ®Google Scholar
• Gomord V, Fitchette AC, Menu‐Bouaouiche L, et al. Plant‐specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J. 2010;8(5):564–587.
   PubMed Web of Science ®Google Scholar
• Bañuelos-Hernández B, Monreal-Escalante E, González-Ortega O. Algevir: an expression system for microalgae based on viral vectors. Front Microbiol. 2017;30(8):1100.
   Google Scholar
• Márquez-Escobar VA, Bañuelos-Hernández B, Rosales-Mendoza S. Expression of a Zika virus antigen in microalgae: towards mucosal vaccine development. J Biotechnol. 2018;282:86–91.
   PubMed Web of Science ®Google Scholar
• Patel VK, Soni N, Prasad V, et al. CRISPR–Cas9 system for genome engineering of photosynthetic microalgae. Mol Biotechnol. 2019;61:541–561.
   PubMed Web of Science ®Google Scholar
• Encarnação T, Pais AA, Campos MG, et al. Cyanobacteria and microalgae: a renewable source of bioactive compounds and other chemicals. Sci Prog. 2015;98(Pt 2):145–168.
   PubMed Web of Science ®Google Scholar
• Carrera-Pacheco SE, Hankamer B. Oey M Optimising light conditions increases recombinant protein production in Chlamydomonas reinhardtii chloroplasts. Algal Res. 2018;32:329–340
   Google Scholar
• Lizzul AM, Lekuona-Amundarain A, Purton S, et al. Characterization of Chlorella sorokiniana, UTEX 1230. Biology (Basel). 2018;7(2):pii: E25.
   PubMedGoogle Scholar
• Loera-Quezada MM, Leyva-González MA, Velázquez-Juárez G, et al. A novel genetic engineering platform for the effective management of biological contaminants for the production of microalgae. Plant Biotechnol J. 2016;14(10):2066–2076.
   PubMed Web of Science ®Google Scholar
• Sandoval-Vargas JM, Macedo-Osorio KS, Durán-Figueroa NV, et al. Chloroplast engineering of Chlamydomonas reinhardtii to use phosphite as phosphorus source. Algal Res. 2018;33:291–297.
   Google Scholar
• Poehlein A, Daniel R, Schink B, et al. Life based on phosphite: a genome-guided analysis of Desulfotignum phosphitoxidans. BMC Genomics. 2013;14(1):753.
   PubMedGoogle Scholar
• Ravi A, Guo S, Rasala B, et al., Separation options for phosphorylated osteopontin from transgenic microalgae Chlamydomonas reinhardtii. Int J Mol Sci. 19(2): pii: E585. 2018.
   Web of Science ®Google Scholar
• Lomonossoff GP, D’Aoust MA. Plant-produced biopharmaceuticals: a case of technical developments driving clinical deployment. Science. 2016;353(6305):1237–1240.
   PubMed Web of Science ®Google Scholar
• Su J, Zhu L, Sherman A, et al. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials. 2015;70:84–93.
   PubMed Web of Science ®Google Scholar
• Gregory JA, Shepley-McTaggart A, Umpierrez M, et al., Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice. Plant Biotechnol J. 14(7): 1541–1550. 2016.
   PubMed Web of Science ®Google Scholar
• Demurtas OC, Massa S, Ferrante P. A Chlamydomonas - derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection. PLoS One. 2013;8(4):e61473.
   PubMed Web of Science ®Google Scholar
• Geng D, Wang Y, Wang P, et al. Stable expression of hepatitis B surface antigen gene in Dunaliella salina (Chlorophyta). J Appl Phycol. 2003;15:451–456.
   Web of Science ®Google Scholar
• Wang XF, Brandsma M, Tremblay R, et al. A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65). BMC Biotechnol. 2008;8:87.
   PubMed Web of Science ®Google Scholar
• Dauvillée D, Delhaye S, Gruyer S, et al. Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules. PLoS One. 2010;5(12):e15424.
   PubMed Web of Science ®Google Scholar
• Gregory JA, Li F, Tomosada LM, et al. Algae produced Pfs25 elicits antibodies that inhibit malaria transmission. PLoS One. 2012;7(5):e37179.
   PubMed Web of Science ®Google Scholar
• Kumar A, Falcao VR, Sayre RT. Evaluating nuclear transgene expression systems in Chlamydomonas reinhardtii. Algal Res. 2013;2(4):321–332.
   Google Scholar
• Soria-Guerra RE, Ramirez-Alonso JI, Ibañez-Salazar A, et al. Expression of an HBcAg-based antigen carrying angiotensin II in Chlamydomonas reinhardtii as a candidate hypertension vaccine. Plant Cell Tissue Organ Cult. 2014;116:133–139.
   Web of Science ®Google Scholar
• Beltrán-López JI, Romero-Maldonado A, Monreal-Escalante E, et al. Chlamydomonas reinhardtii chloroplasts express an orally immunogenic protein targeting the p210 epitope implicated in atherosclerosis immunotherapies. Plant Cell Rep. 2016;35(5):1133–1141.
   PubMed Web of Science ®Google Scholar
• Hirschl S, Ralser C, Asam C, et al. Expression and characterization of functional recombinant Bet v 1.0101 in the chloroplast of Chlamydomonas reinhardtii. Int Arch Allergy Immunol. 2017;173(1):44–50.
   PubMed Web of Science ®Google Scholar
• Shamriz S, Ofoghi H. Engineering the chloroplast of Chlamydomonas reinhardtii to express the recombinant PfCelTOS-Il2 antigen-adjuvant fusion protein. J Biotechnol. 2018;266:111–117.
   PubMed Web of Science ®Google Scholar
• Feng S, Feng W, Zhao L, et al. Preparation of transgenic Dunaliella salina for immunization against white spot syndrome virus in crayfish. Arch Virol. 2014;159:519–525.
   PubMed Web of Science ®Google Scholar
• Tran M, Van C, Barrera DJ, et al., Production of unique immunotoxin cancer therapeutics in algal chloroplasts. Proc Natl Acad Sci USA. 110(1): E15–E22. 2013.
   PubMed Web of Science ®Google Scholar
• Barrera DJ, Rosenberg JN, Chiu JG, et al., Algal chloroplast produced camelid VH H antitoxins are capable of neutralizing botulinum neurotoxin. Plant Biotechnol J. 13(1): 117–124. 2015.
   PubMed Web of Science ®Google Scholar
• Sun M, Qian K, Su N, et al. Foot-and-mouth disease virus VP1 protein fused with cholera toxin B subunit expressed in Chlamydomonas reinhardtii chloroplast. Biotechnol Lett. 2003;25:1087–1092.
   PubMed Web of Science ®Google Scholar
• He DM, Qian KX, Shen GF, et al. Recombination and expression of classical swine fever virus (CSFV) structural protein E2 gene in Chlamydomonas reinhardtii chroloplasts. Colloids Surf B Biointerfaces. 2007;55:26–30.
   PubMed Web of Science ®Google Scholar
• Yang Z, Wang J, Cheng X, et al. Making porcine circovirus vaccine to prevent/treat porcine circovirus infection involves coding porcine circovirus type 2 antigen gene in Chlamydomonas chloroplasts, constructing chloroplasts in expression box; selecting antigen; screening. Patent CN103007269-A. 2013.
   Google Scholar
• Davis A, Crum LT, Corbeil LB, et al. Expression of Histophilus somni IbpA DR2 protective antigen in the diatom Thalassiosira pseudonana. Appl Microbiol Biotechnol. 2017;101(13):5313–5324.
   PubMed Web of Science ®Google Scholar
• Hempel F, Lau J, Klingl A, et al. Algae as protein factories: expression of a human antibody and the respective antigen in the diatom Phaeodactylum tricornutum. PLoS One. 2011;6(12):e28424.
   PubMed Web of Science ®Google Scholar
• Vanier G, Stelter S, Vanier J, et al. Alga-made anti-Hepatitis B antibody binds to human fcγ receptors. Biotechnol J. 2018;13(4):e1700496.
   PubMed Web of Science ®Google Scholar
• Stoffels L, Taunt HN, Charalambous B, et al. Synthesis of bacteriophage lytic proteins against Streptococcus pneumoniae in the chloroplast of Chlamydomonas reinhardtii. Plant Biotechnol J. 2017;15(9):1130–1140.
   PubMed Web of Science ®Google Scholar
• Rasala BA, Muto M, Lee PA, et al. Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtii. Plant Biotechnol J. 2010;8(6):719–733.
   PubMed Web of Science ®Google Scholar
• Chávez MN, Schenck TL, Hopfner U, et al. Towards autotrophic tissue engineering: photosynthetic gene therapy for regeneration. Biomaterials. 2016;75:25–36.
   PubMed Web of Science ®Google Scholar
• Xue L, Pan W, Jiang G, et al. Transgenic Dunaliella salina as a bioreactor. US patent application. US20030066107 A1. 2003.
   Google Scholar
• Yang Z, Lih Y, Chen F, et al. Expression of human soluble TRAIL in Chlamydomonas reinhardtii chloroplast. Chin Sci Bull. 2006;51(14):1703–1709.
   Google Scholar
• Somchai P, Jitrakorn S, Thitamadee S, et al. Use of microalgae Chlamydomonas reinhardtii for production of double-stranded RNA against shrimp virus. Aquacult Rep. 2016;3:178–183.
   Web of Science ®Google Scholar
• Kim DH, Kim YT, Cho JJ, et al. Stable integration and functional expression of flounder growth hormone gene in transformed microalga, Chlorella ellipsoidea. Mar Biotechnol. 2002;4(1):63–73.
   PubMed Web of Science ®Google Scholar
• Li SS, Tsai HJ. Transgenic microalgae as a non-antibiotic bactericide producer to defend against bacterial pathogen infection in the fish digestive tract. Fish Shellfish Immunol. 2009;26(2):316–325.
   PubMed Web of Science ®Google Scholar
• Hawkins RL, Nakamura M. Expression of human growth hormone by the eukaryotic alga, Chlorella. Curr Microbiol. 1999;38(6):335–341.
   PubMed Web of Science ®Google Scholar
• Chen Y, Wang YQ, Sun YR, et al. Highly efficient expression of rabbit neutrophil peptide-1 gene in Chlorella ellipsoidea cells. Curr Genet. 2001;39(5–6):365–370.
   PubMed Web of Science ®Google Scholar
• Eichler-Stahlberg A, Weisheit W, Ruecker O, et al. Strategies to facilitate transgene expression in Chlamydomonas reinhardtii. Planta. 2009;229(4):873–883.
   PubMed Web of Science ®Google Scholar
• Michelet L, Lefebvre-Legendre L, Burr SE, et al. Enhanced chloroplast transgene expression in a nuclear mutant of Chlamydomonas. Plant Biotechnol J. 2011;9:565–574.
   PubMed Web of Science ®Google Scholar
• Chai XJ, Chen HX, Xu WQ, et al. Expression of soybean Kunitz trypsin inhibitor gene SKTI in Dunaliella salina. J Appl Phycol. 2013;25(1):139–144.
   Web of Science ®Google Scholar
• Wannathong T, Waterhouse JC, Young RE, et al. New tools for chloroplast genetic engineering allow the synthesis of human growth hormone in the green alga Chlamydomonas reinhardtii. Appl Microbiol Biotechnol. 2016;100(12):5467–5477.
   PubMed Web of Science ®Google Scholar
• Faè M, Accossato S, Cella R, et al. Comparison of transplastomic Chlamydomonas reinhardtii and Nicotiana tabacum expression system for the production of a bacterial endoglucanase. Appl Microbiol Biotechnol. 2017;101(10):4085–4092.
   PubMed Web of Science ®Google Scholar
• Dong B, Cheng RQ, Liu QY, et al. Multimer of the antimicrobial peptide Mytichitin-A expressed in Chlamydomonas reinhardtii exerts a broader antibacterial spectrum and increased potency. J Biosci Bioeng. 2017b;125(2):175–179.
   PubMed Web of Science ®Google Scholar
• Baier T, Kros D, Feiner RC, et al. Engineered fusion proteins for efficient protein secretion and purification of a human growth factor from the green microalga Chlamydomonas reinhardtii. ACS Synth Biol. 2018a;7(11):2547–2557.
   PubMed Web of Science ®Google Scholar
• Dreesen IA, Charpin-El, Hamri G, Fussenegger M. Heat-stable oral alga-based vaccine protects mice from Staphylococcus aureus infection. J Biotechnol. 2010;145:273–280.
   PubMed Web of Science ®Google Scholar
• Gregory JA, Topol AB, Doerner DZ, et al. Alga-produced cholera toxin-Pfs25 fusion proteins as oral vaccines. Appl Environ Microbiol. 2013;79(13):3917–3925.
   PubMed Web of Science ®Google Scholar
• Roth J, Zuber C, Park S, et al. Protein N-glycosylation, protein folding, and protein quality control. Mol Cells. 2010;30(6):497–506.
   PubMed Web of Science ®Google Scholar
• Van Ree R, Cabanes-Macheteau M, Akkerdaas J, et al. Beta (1,2)-xylose and alpha (1,3)-fucose residues have a strong contribution in IgE binding to plant glycoallergens. J Biol Chem. 2000;275(15):11451–11458.
   PubMed Web of Science ®Google Scholar
• Shaaltiel Y, Bartfeld D, Hashmueli S, et al. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J. 2007;5(5):579–590.
   PubMed Web of Science ®Google Scholar
• Bosch D, Schots A. Plant glycans: friend or foe in vaccine development? Expert Rev Vaccines. 2010;9(8):835–842.
   PubMed Web of Science ®Google Scholar
• Wang Q, Yin B, Chung CY, et al. Glycoengineering of CHO cells to improve product quality. Methods Mol Biol. 2017;1603:25–44.
   PubMedGoogle Scholar
• Cockburn I, Long G. The importance of patents to innovation: updated cross-industry comparisons with biopharmaceuticals. Expert Opin Ther Pat. 2015;25(7):739–742.
   PubMed Web of Science ®Google Scholar
• Chichester JA, Green BJ, Jones RM, et al. Safety and immunogenicity of a plant-produced Pfs25 virus-like particle as a transmission blocking vaccine against malaria: a Phase 1 dose-escalation study in healthy adults. Vaccine. 2018;36(39):5865–5871.
   PubMed Web of Science ®Google Scholar
• Mor TS. Molecular pharming’s foot in the FDA’s door: protalix’s trailblazing story. Biotechnol Lett. 2015;37(11):2147–2150.
   PubMed Web of Science ®Google Scholar
• Pillet S, Aubin É, Trépanier S, et al. Humoral and cell-mediated immune responses to H5N1 plant-made virus-like particle vaccine are differentially impacted by alum and GLA-SE adjuvants in a Phase 2 clinical trial. NPJ Vaccines. 2018;3:3.
   PubMed Web of Science ®Google Scholar
• Kesik-Brodacka M. Progress in biopharmaceutical development. Biotechnol Appl Biochem. 2018;65(3):306–322.
   PubMed Web of Science ®Google Scholar
• McCamish M, Yoon W, McKay J. Biosimilars: biologics that meet patients’ needs and healthcare economics. Am J Manag Care. 2016;22(13 Suppl):S439–S442.
   PubMed Web of Science ®Google Scholar
• Stevenson JG. Clinical data and regulatory issues of biosimilar products. Am J Manag Care. 2015;21(16 Suppl):s320–s330.
   PubMed Web of Science ®Google Scholar
• Daller J. Biosimilars: a consideration of the regulations in the united states and european union. Regul Toxicol Pharmacol. 2016;76:199–208.
   PubMed Web of Science ®Google Scholar
• Klimyuk V, Pogue G, Herz S, et al. Production of recombinant antigens and antibodies in Nicotiana benthamiana using ‘magnifection’technology: GMP-compliant facilities for small-and large-scale manufacturing. Curr Top Microbiol Immunol. 2014;375:127–154.
   Google Scholar
• Pillet S, Couillard J, Trépanier S, et al. Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate—Two randomized Phase II clinical trials in 18 to 49 and≥ 50 years old adults. PloS One. 2019;14(6):e0216533.
   PubMed Web of Science ®Google Scholar