Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells

Advanced Drug Delivery Reviews

Volumn 65, Issue 6, 2013, Pages 782-799

  Kwon, Kwang Chul ^a   Verma, Dheeraj ^a   Singh, Nameirakpam D ^a   Herzog, Roland ^b   Daniell, Henry ^a  

^a UNIVERSITY OF CENTRAL FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Autoantigens; Bioencapsulation; Diabetes; Hemophilia; Infectious diseases; Lyophilization; Molecular farming; Oral vaccines

Indexed keywords

AUTOANTIGENS; BIOENCAPSULATION; HEMOPHILIA; INFECTIOUS DISEASE; LYOPHILIZATION; MOLECULAR FARMING;

BLOOD; MEDICAL PROBLEMS; PLANT CELL CULTURE; PROTEINS; VACCINES;

ANTIGENS;

AUTOANTIGEN; BIS (3',5') CYCLIC DIMERIC GUANOSINE; BLOOD CLOTTING FACTOR 9; BLOOD CLOTTING FACTOR 9 COMPLEX; BLOOD CLOTTING FACTOR 9 CONCENTRATE; CHOLERA TOXIN B SUBUNIT; CHOLERA VACCINE; CYCLIC GMP; ENFUVIRTIDE; EXENDIN 4; FODRIN; INSULIN; LEUPRORELIN; MACROGOL; MALARIA VACCINE; NONAFACTOR; PROINSULIN; RECOMBINANT BLOOD CLOTTING FACTOR 9; RECOMBINANT PROTEIN; SODIUM CHLORIDE; TRIPROLIDINE; UNCLASSIFIED DRUG; VACCINE;

ANTIBODY TITER; BACTERIUM; CELL ENCAPSULATION; CHOLERA; CRYOPRESERVATION; DRUG ADMINISTRATION ROUTE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; ENZYME REGULATION; ENZYME RELEASE; FREEZE DRYING; GLOMERULONEPHRITIS; GLUCOSE BLOOD LEVEL; HEMOPHILIA; HEMOPHILIA B; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOCOMPETENT CELL; IMMUNOTHERAPY; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; MALARIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLAGUE; PLANT CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTOZOON; PURIFICATION; REVIEW; SJOEGREN SYNDROME; VIRUS;

ADMINISTRATION, ORAL; AUTOANTIGENS; BIOLOGICAL AVAILABILITY; BLOOD GLUCOSE; CHOLERA VACCINES; DIABETES MELLITUS; DRUG CARRIERS; FACTOR IX; FREEZE DRYING; GASTROINTESTINAL TRACT; HUMANS; MALARIA VACCINES; PEPTIDES; PLAGUE VACCINE; PLANT CELLS; PROINSULIN; PROTEINS; VACCINES; VENOMS;

EID: 84878850344     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2012.10.005     Document Type: Review

References (206)

1. Engaging communities to improve global health: reducing disease burden through collaborative approaches 2010, http://conferences.thehillgroup.com/obssr/engagingcommunities/about.html, The Hill Group, (Johannesburg and Durban).
2. Daniell H., Singh N.D., Mason H., Streatfield S.J. Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci. 2009, 14:669-679.
3. Nitesh S.C., Sanjeev C., Vandana H., Alka A., Vijender S. Recent advances in insulin delivery systems: an update. World Appl. Sci. J. 2010, 11:1552-1556.
4. Akhrass F., Skinner N., Boswell K., Travis L.B. Evolving trends in insulin delivery: in pursuit of improvements in diabetes management. AHDB 2010, 3:117-122.
5. Kermode M. Unsafe injections in low-income country health settings: need for injection safety promotion to prevent the spread of blood-borne viruses. Health Promot. Int. 2004, 19:95-103.
6. Report of the SIGN 2010 meeting: annual meeting of the safe injection global network, Dubai 2010, http://www.who.int/injection_safety/toolbox/sign2010_meeting.pdf.
7. Lebre F., Borchard G., Conceição Pedroso de Lima M., Borges O. Progress towards a needle-free hepatitis B vaccine. Pharm. Res. 2011, 28:986-1012.
8. Ruhlman T., Verma D., Samson N., Daniell H. The role of heterologous chloroplast sequence elements in transgene integration and expression. Plant Physiol. 2010, 152:2088-2104.
9. 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. 2005, 73:8266-8274.
10. Watson J., Koya V., Leppla S.H., Daniell H. Expression of Bacillus anthracis protective antigen in transgenic chloroplasts of tobacco, a non-food/feed crop. Vaccine 2004, 22:4374-4384.
11. Daniell H. Molecular strategies for gene containment in transgenic crops. Nat. Biotechnol. 2002, 20:581-586.
12. Daniell H. Transgene containment by maternal inheritance: effective or elusive?. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:6879-6880.
13. De Cosa B., Moar W., Lee S.B., Miller M., Daniell H. Overexpression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals. Nat. Biotechnol. 2001, 19:71-74.
14. Quesada-Vargas T., Ruiz O.N., Daniell H. Characterization of heterologous multigene operons in transgenic chloroplasts: transcription, processing, and translation. Plant Physiol. 2005, 138:1746-1762.
15. Kumar S., Hahn F.M., Baidoo E., Kahlon T.S., Wood D.F., McMahan C.M., Cornish K., Keasling J.D., Daniell H., Whalen M.C. Remodeling the isoprenoid pathway in tobacco by expressing the cytoplasmic mevalonate pathway in chloroplasts. Metab. Eng. 2012, 14:19-28.
16. Davoodi-Semiromi A., Schreiber M., Nalapalli 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. 2010, 8:223-242.
17. Kanagaraj A.P., Verma D., Daniell H. Expression of dengue-3 premembrane and envelope polyprotein in lettuce chloroplasts. Plant Mol. Biol. 2011, 76:323-333.
18. 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. 2008, 76:3640-3650.
19. Ruhlman T., Ahangari R., Devine A., Samsam M., Daniell H. Expression of cholera toxin B-proinsulin fusion protein in lettuce and tobacco chloroplasts - oral administration protects against development of insulitis in non-obese diabetic mice. Plant Biotechnol. J. 2007, 5:495-510.
20. 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. 2011, 9:585-598.
21. 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-alpha2b. Plant Biotechnol. J. 2007, 5:511-525.
22. 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. 2009, 9:33.
23. 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. 2011, 9:100-115.
24. Ruiz O.N., Alvarez D., Torres C., Roman L., Daniell H. Metallothionein expression in chloroplasts enhances mercury accumulation and phytoremediation capability. Plant Biotechnol. J. 2011, 9:609-617.
25. K.C. Kwon, R. Nityanandam, J.S. New, H. Daniell, 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. (in press), http://dx.doi.org/10.1111/pbi.12008.
26. Pelosi A., Shepherd R., Walmsley A.M. Delivery of plant-made vaccines and therapeutics. Biotechnol. Adv. 2012, 30:440-448.
27. Newman K.D., Elamanchili P., Kwon G.S., Samuel J. Uptake of poly (d,l-lactic-co-glycolic acid) microspheres by antigen-presenting cells in vivo. J. Biomed. Mater. Res. 2002, 60:480-486.
28. Kroger A.T., Sumaya C.V., Pickering L.K., Atkinson W.L. General recommendations on immunization: recommendations of the advisory committee on immunization practices (ACIP) 2011, http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm.
29. Harper S.A., Fukuda K., Uyeki T.M., Cox N.J., Bridges C.B. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 2005, 54:1-40.
30. Ruben F.L., Jackson G.G. A new subunit influenza vaccine: acceptability compared with standard vaccines and effect of dose on antigenicity. J. Infect. Dis. 1972, 125:656-664.
31. Brown H., Kasel J.A., Freeman D.M., Moise L.D., Grose N.P., Couch R.B. The immunizing effect of influenza A/New Jersey/76 (Hsw1N1) virus vaccine administered intradermally and intramuscularly to adults. J. Infect. Dis. 1977, 136:S466-S471.
32. Mantoux C. L'intradermo-reaction a la tuberculine et son interpretation clinique. Presse Med. 1910, 18:10-13.
33. Nirmal S., Cherian T., Samuel B.U., Rajasingh J., Raghupathy P., John T.J. Immune response of infants to fractional doses of intradermally administered inactivated poliovirus vaccine. Vaccine 1998, 16:928-931.
34. Cone R.A. Barrier properties of mucus. Adv. Drug Deliv. Rev. 2009, 61:75-85.
35. Park K., Kwon I.C., Park K. Oral protein delivery: current status and future prospect. React. Funct. Polym. 2011, 71:344-349.
36. Khafagy E.S., Morishita M., Onuki Y., Takayama K. Current challenges in non-invasive insulin delivery systems: a comparative review. Adv. Drug Deliv. Rev. 2007, 59:1521-1546.
37. Jadhav K.R., Gambhire M.N., Shaikh I.M., Kadam V.J., Pisal S.S. Nasal drug delivery system-factors affecting and applications. Curr. Drug Ther. 2007, 2:27-38.
38. Varshosaz J., Sadrai H., Alinagari R. Nasal delivery of insulin using chitosan microspheres. J. Microencapsul. 2004, 21:761-774.
39. Varshosaz J., Sadrai H., Heidari A. Nasal delivery of insulin using bioadhesive chitosan gels. Drug Deliv. 2006, 13:31-38.
40. Veuillez F., Kalia Y.N., Jacques Y., Deshusses J., Buri P. Factors and strategies for improving buccal absorption of peptides. Eur. J. Pharm. Biopharm. 2001, 51:93-109.
41. Sudhakar Y., Kuotsu K., Bandyopadhyay A.K. Buccal bioadhesive drug delivery - a promising option for orally less efficient drugs. J. Control. Release 2006, 114:15-40.
42. Kumria R., Goomber G. Emerging trends in insulin delivery: buccal route. J. Diabetol. 2011, 2:1.
43. Yang T.Z., Wang X.T., Yan X.Y., Zhang Q. Phospholipid deformable vesicles for buccal delivery of insulin. Chem. Pharm. Bull. 2002, 50:749-753.
44. Luo Y., Xu H., Huang K., Gao J., Peng H., Sheng X. Study on nanoparticle system for buccal delivery of insulin. Conf. Proc. IEEE Eng. Med. Biol. 2005, 5:4842-4845.
45. Hosny E.A., Elkheshen S.A., Saleh S.I. Buccoadhesive tablets for insulin delivery: in vitro and in vivo studies. Boll. Chim. Farm. 2002, 141:210-217.
46. Sahni J., Raj S., Ahmad F.J., Khar R.K. Design and in vitro characterization of buccoadhesive drug delivery system of insulin. Indian J. Pharm. Sci. 2008, 70:61-65.
47. Portero A., Teijeiro-Osorio T., Alonso M.J., Remuñán-López C. Development of chitosan sponges for buccal administration of insulin. Carbohydr. Polym. 2007, 68:617-625.
48. Xu B.H., Huang K.X., Zhu Y.S., Gao Q.H., Wu Q.Z., Tian W.Q., Sheng X.Q., Chen Z.X., Gao Z.H. Hypoglycaemic effect of a novel insulin buccal formulation on rabbits. Pharmacol. Res. 2002, 46:459-467.
49. Cui F., He C., He M., Tang C., Yin L., Qian F., Yin C. Preparation and evaluation of chitosan-ethylenediaminetetraacetic acid hydrogel films for the mucoadhesive transbuccal delivery of insulin. J. Biomed. Mater. Res. A 2009, 89:1063-1071.
50. Zhang Y., Zhu J., Tang Y., Chen X., Yang Y. The preparation and application of pulmonary surfactant nanoparticles as absorption enhancers in insulin dry powder delivery. Drug Dev. Ind. Pharm. 2009, 9:1059-1065.
51. Klingler C., Müller B.W., Steckel H. Insulin-micro- and nanoparticles for pulmonary delivery. Int. J. Pharm. 2009, 377:173-179.
52. http://www.gurufocus.com.
53. Prausnitz M.R., Langer R. Transdermal drug delivery. Nat. Biotechnol. 2008, 26:1261-1268.
54. Prausnitz M.R. Overcoming skin's barrier: the search for effective and user-friendly drug delivery. Diabetes Technol. Ther. 2001, 3:233-236.
55. Kirschner N., Houdek P., Fromm M., Moll I., Brandner J.M. Tight junctions form a barrier in human epidermis. Eur. J. Cell Biol. 2010, 89:839-842.
56. Pillai O., Nair V., Panchagnula R. Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers. Int. J. Pharm. 2004, 269:109-120.
57. Rastogi R., Anand S., Dinda A.K., Koul V. Investigation on the synergistic effect of a combination of chemical enhancers and modulated iontophoresis for transdermal delivery of insulin. Drug Dev. Ind. Pharm. 2010, 36:993-1004.
58. Boucaud A., Garrgue M.A., Machet L., Vaillant L., Patat F. Effect of sonication parameters on transdermal of insulin to hairless rats. J. Control. Release 2002, 81:113-119.
59. Levin G. Advances in radio-frequency transdermal drug delivery. Pharm. Technol. 2008, 32:s12-s19.
60. Lee K., Lee H.C., Lee D.S., Jung H. Drawing lithography: three dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Adv. Mater. 2010, 22:483-486.
61. Gupta J., Felner E.I., Prausnitz M.R. Minimally invasive insulin delivery in subjects with type I diabetes using hollow microneedles. Diabetes Technol. Ther. 2009, 11:329-337.
62. Andrews S., Lee J.W., Prausnitz M. Recovery of skin barrier after stratum corneum removal by microdermabrasion. AAPS PharmSciTech 2011, 12:1393-1400.
63. http://www.Phosphagenics.com.
64. Weiner H.L., da Cunha A.P., Quintana F., Wu H. Oral tolerance. Immunol. Rev. 2011, 241:241-259.
65. Gong Z., Jin Y., Zhang Y. Oral administration of a cholera toxin B subunit-insulin fusion protein produced in silkworm protects against autoimmune diabetes. J. Biotechnol. 2005, 119:93-105.
66. Denes B., Krausova V., Fodor N., Timiryasova T., Henderson D., Hough J., Yu J., Fodor I., Langridge W.H. Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens. J. Immunother. 2005, 28:438-448.
67. Gong Z., Pan L., Le Y., Liu Q., Zhou M., Xing W., Zhuo R., Wang S., Guo J. Glutamic acid decarboxylase epitope protects against autoimmune diabetes through activation of Th2 immune response and induction of possible regulatory mechanism. Vaccine 2010, 28:4052-4058.
68. Ma S.W., Zhao D.L., Yin Z.Q., Mukherjee R., Singh B., Qin H.Y., Stiller C.R., Jevnikar A.M. Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance. Nat. Med. 1997, 3:793-796.
69. Ma S., Huang Y., Yin Z., Menassa R., Brandle J.E., Jevnikar A.M. Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:5680-5685.
70. Takagi H., Hiroi T., Yang L., Tada Y., Yuki Y., Takamura K., Ishimitsu R., Kawauchi H., Kiyono H., Takaiwa F. A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:17525-17530.
71. Suzuki K., Kaminuma O., Yang L., Takai T., Mori A., Umezu-Goto M., Ohtomo T., Ohmachi Y., Noda Y., Hirose S., Okumura K., Ogawa H., Takada K., Hirasawa M., Hiroi T., Takaiwa F. Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression. Plant Biotechnol. J. 2011, 9:982-990.
72. Takagi H., Hiroi T., Yang L., Takamura K., Ishimitsu R., Kawauchi H., Takaiwa F. Efficient induction of oral tolerance by fusing cholera toxin B subunit with allergen-specific T-cell epitopes accumulated in rice seed. Vaccine 2008, 26:6027-6030.
73. Arakawa T., Yu J., Chong D.K., Hough J., Engen P.C., Langridge W.H. A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes. Nat. Biotechnol. 1998, 16:934-938.
74. Upadhyay S., Parikh A., Joshi P., Upadhyay U.M., Chotai N.P. Intranasal drug delivery system - a glimpse to become maestro. J. Appl. Pharm. Sci. 2011, 1:34-44.
75. Reynolds J., Prodromidi E.I., Juggapah J.K., Abbott D.S., Holthaus K.A., Kalluri R., Pusey C.D. Nasal administration of recombinant rat alpha3(IV)NC1 prevents the development of experimental autoimmune glomerulonephritis in the WKY rat. J. Am. Soc. Nephrol. 2005, 16:1350-1359.
76. He J., Zhao J., Li Z. Mucosal administration of alpha-fodrin inhibits experimental Sjögren's syndrome autoimmunity. Arthritis Res. Ther. 2008, 10:R44.
77. Zhao J., Li R., He J., Shi J., Long L., Li Z. Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells. Rheumatol. Int. 2008, 29:9-16.
78. Cao O., Armstrong E., Schlachterman A., Wang L., Okita D.K., Conti-Fine B., High K.A., Herzog R.W. Immune deviation by mucosal antigen administration suppresses gene-transfer- induced inhibitor formation to factor IX. Blood 2006, 108:480-486.
79. Rawle F.E., Pratt K.P., Labelle A., Weiner H.L., Hough C., Lillicrap D. Induction of partial immune tolerance to factor VIII through prior mucosal exposure to the factor VIII C2 domain. J. Thromb. Haemost. 2006, 4:2172-2179.
80. Kobayashi M., Abiru N., Arakawa T., Fukushima K., Zhou H., Kawasaki E., Yamasaki H., Liu E., Miao D., Wong F.S., Eisenbarth G.S., Eguchi K. Altered B:9-23 insulin, when administered intranasally with cholera toxin adjuvant, suppresses the expression of insulin autoantibodies and prevents diabetes. J. Immunol. 2007, 179:2082-2088.
81. Wang H., Yang J., Jin L., Feng J., Lu Y., Sun Y., Li T., Cao R., Wu J., Fan H., Liu J. Immunotherapy of autoimmune diabetes by nasal administration of tandem glutamic acid decarboxylase 65 peptides. Immunol. Invest. 2009, 38:690-703.
82. O'Hagan D.T., Rappuoli R. Novel approaches to vaccine delivery. Pharm. Res. 2004, 21(9):1519-1530.
83. McGhee J.R., Lamm M.E., Strober W. Mucosal immune responses: an overview. Mucosal Immunology 1999, 485-506. Academic Press, San Diego. P.L. Ogra, J. Mestecky, M.E. Lamm, W. Strober, J. Bienenstock, J.R. McGhee (Eds.).
84. MacPherson A., McCoy K., Johansen F.E., Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol. 2008, 1:11-22.
85. Neutra M., Kozlowski P. Mucosal vaccines: the promise and the challenge. Nat. Rev. Immunol. 2006, 6:148-158.
86. Dukes C., Bussey H.J.R. The number of lymphoid follicles of the human large intestine. J. Pathol. 1926, 29:111-116.
87. Neutra M., Mantis N., Kraehenbuhl J. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat. Immunol. 2001, 2:1004-1009.
88. McGhee J.R., Mestecky J., Dertzbaugh M.T., Eldridge J.H., Hirasawa M., Kiyono H. The mucosal immune system: from fundamental concepts to vaccine development. Vaccine 1992, 10:75-88.
89. Martin-Villa J.M., Ferre-Lopez S., Lopez-Suarez J.C., Corell A., Perez-Blas M., Arnaiz-Villena A. Cell surface phenotype and ultramicroscopic analysis of purified human enterocytes: a possible antigen-presenting cell in the intestine. Tissue Antigens 1997, 50:586-592.
90. Rodriguez-Juan C., Perez-Blas M., Suarez-Garcia E., Lopez-Suarez J.C., Muzquiz M., Cuadrado C., Martín-Villa J.M. Lens culinaris, Phaseolus vulgaris and Vicia faba lectins specifically trigger IL-8 production by the human colon carcinoma cell line CACO-2. Cytokine 2000, 12:1284-1287.
91. Rodriguez-Juan C., Perez-Blas M., Valeri A.P., Aguilera N., Arnaiz-Villena A., Pacheco-Castro A., Martin-Villa J.M. Cell surface phenotype andcytokine secretion in Caco-2 cell cultures: increased RANTES production and IL-2 transcription upon stimulation with IL-1beta. Tissue Cell 2001, 33:570-579.
92. Medina E., Guzman C.A. Modulation of immune responses following antigen administration by mucosal route. FEMS Immunol. Med. Microbiol. 2000, 27:305-311.
93. Nochi T., Takagi H., Yuki Y., Yang L., Masumura T., Mejima M., Nakanishi U., Matsumura A., Uozumi A., Hiroi T., Morita S., Tanaka K., Takaiwa F., Kiyono H. Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:10986-10991.
94. Amani J., Mousavi S.L., Rafati S., Salmanian A.H. Immunogenicity of a plant-derived edible chimeric EspA, Intimin and Tir of Escherichia coli O157:H7 in mice. Plant Sci. 2011, 180:620-627.
95. Streatfield S. Mucosal immunization using recombinant plant-based oral vaccines. Methods 2006, 38:150-157.
96. Haglund K., Leiner I., Kerksiek K., Buonocore L., Pamer E., Rose J.K. Robust recall and long-term memory T-cell responses induced by prime-boost regimens with heterologous live viral vectors expressing Human immunodeficiency virus type 1 Gag and Env proteins. J. Virol. 2002, 76:7506-7517.
97. Hayden C.A., Streatfield S.J., Lamphear B.J., Fake G.M., Keener T.K., Walker J.H., Clements J.D., Turner D.D., Tizard I.R., Howard J.A. Bioencapsulation of the hepatitis B surface antigen and its use as an effective oral immunogen. Vaccine 2012, 30:2937-2942.
98. Pal R., Wang S., Kalyanaraman V.S., Nair B.C., Whitney S., Keen T., Hocker L., Hudacik L., Rose N., Cristillo A., Mboudjeka I., Shen S., Wu-Chou T., Montefiori D., Mascola J., Lu S., Markham P. Polyvalent DNA prime and envelope protein boost HIV-1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate. J. Med. Primatol. 2005, 34:226-236.
99. Almeida A.J., Alpar H.O. Nasal delivery of vaccines. J. Drug Target. 1996, 3:455-467.
100. Neutra R.M., Pringault E., Kraehenbuhl J.P. Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annu. Rev. Immunol. 1996, 14:275-300.
101. Jahnsen F.L., Gran E., Haye R., Brandtzaeg P. Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes. Am. J. Respir. Cell Mol. Biol. 2004, 30:31-37.
102. Suman J.D. Nasal drug delivery. Expert Opin. Biol. Ther. 2003, 3:519-523.
103. Wang B.Z., Xu R., Quan F.S., Kang S.M., Wang L., Compans R.W. Intranasal immunization with influenza VLPs incorporating membrane-anchored flagellin induces strong heterosubtypic protection. PLoS One 2010, 5:e13972.
104. Madhun A.S., Haaheim L.R., Nostbakken J.K., Ebensen T., Chichester J., Yusibov V., Guzman C.A., Cox R.J. Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice. Vaccine 2011, 29:4973-4982.
105. Gor D.O., Rose N.R., Greenspan N.S. TH1-TH2: a procrustean paradigm. Nat. Immunol. 2003, 4:503-505.
106. Zhu J., Yamane H., Paul W.E. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 2010, 28:445-489.
107. Freytag L.C., Clements J.D. Mucosal adjuvants. Vaccine 2005, 23:1804-1813.
108. Fujihashi K., Koga T., van Ginkel F.W., Hagiwara Y., McGhee J.R. A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin based adjuvants. Vaccine 2002, 20:2431-2438.
109. Thompson A.L., Staats H.F. Cytokines: the future of intranasal vaccine adjuvants. Clin. Dev. Immunol. 2011, 2011. (Article ID 289597). 10.1155/2011/289597.
110. Limaye A., Koya V., Samsam M., Daniell H. Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system. FASEB J. 2006, 20:959-961.
111. Verma D., Daniell H. Chloroplast vector systems for biotechnology applications. Plant Physiol. 2007, 145:1129-1143.
112. 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. U. S. A. 2010, 107:7101-7106.
113. Patel Y.R. Drug delivery in diabetes: making effective treatment tolerable, ONdrugDelivery 2006, 4-7. http://www.ondrugdelivery.com/publications/diabetes.pdf.
114. Wahren J., Ekberg K., Jörnvall H. C-peptide is a bioactive peptide. Diabetologia 2007, 50:503-509.
115. Insulin delivery systems market forecast to 2014 2012, http://www.rncos.com/Report/IM369.htm.
116. Bellmann-Sickert K., Beck-Sickinger A.G. Peptide drugs to target G protein-coupled receptors. Trends Pharmacol. Sci. 2010, 31:434-441.
117. McGregor D.P. Discovering and improving novel peptide therapeutics. Curr. Opin. Pharmacol. 2008, 8:616-619.
118. Lax R. The future of peptide development in the pharmaceutical industry, PharManufacturing 2012, http://www.polypeptide.com/assets/002/5188.pdf.
119. Diago M., Crespo J., Olveira A., Pérez R., Bárcena R., Sánchez-Tapias J.M., Muñoz-Sánchez M., Romero-Gómez M. Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients. Aliment. Pharmacol. Ther. 2007, 26:1131-1138.
120. Kumar T.R., Soppimath K., Nachaegari S.K. Novel delivery technologies for protein and peptide therapeutics. Curr. Pharm. Biotechnol. 2006, 7:261-276.
121. Baggio L.L., Huang Q., Brown T.J., Drucker D.J. A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes 2004, 53:2492-2500.
122. Subramanian G.M., Fiscella M., Lamouse'-Smith A., Zeuzem S., McHutchison J.G. Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic Hepatitis C. Nat. Biotechnol. 2007, 25:1411-1419.
123. Werle M., Bernkop-Schnurch A. Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids 2006, 30:351-367.
124. Taylor N.A., Van De Ven W.J., Creemers J.W. Curbing activation: proprotein convertases in homeostasis and pathology. FASEB J. 2003, 17:1215-1227.
125. Kim W., Egan J.M. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol. Rev. 2008, 60:470-512.
126. Nielsen L.L., Young A.A., Parkes D.G. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul. Pept. 2004, 117:77-88.
127. Davidson M.B., Bate G., Kirkpatrick P. Exenatide. Nat. Rev. Drug Discov. 2005, 4:713-714.
128. Rowe P.A., Campbell-Thompson M.L., Schatz D.A., Atkinson M.A. The pancrease in human type 1 diabetes. Semin. Immunopathol. 2011, 33:29-43.
129. Zhang L., Nakayama M., Eisenbarth G.S. Insulin as an autoantigen in NOD/human diabetes. Curr. Opin. Immunol. 2008, 20:111-118.
130. Atkinson M.A., Leiter E.H. The NOD mouse model of type 1 diabetes: as good as it gets?. Nat. Med. 1999, 5:601-604.
131. Luo X., Herold K.C., Miller S.D. Immunotherapy of type 1 diabetes: where are we and where should we be going?. Immunity 2010, 32:488-499.
132. Sun J.B., Czerkinsky C., Holmgren J. Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit. Scand. J. Immunol. 2010, 71:1-11.
133. Jenkins P.V., Keenan C., Keeney S., Cumming T., O'Donnell J.S. Clinical utility gene card for: Haemophilia B. Eur. J. Hum. Genet. 2012, 20. 10.1038/ejhg.2011.268.
134. Gater A., Thomson T.A., Strandberg-Larsen M. Haemophilia B: impact on patients and economic burden of disease. Thromb. Haemost. 2011, 106:398-404.
135. DiMichele D. Inhibitor development in Haemophilia B: an orphan disease in need of attention. Br. J. Haematol. 2007, 138:305-315.
136. Ghosh K., Shetty S. Immune response to FVIII in hemophilia A: an overview of risk factors. Clin. Rev. Allergy Immunol. 2009, 37:58-66.
137. Serban M., Mihailov D., Pop L., Ionita H., Ursu E., Talpos-Niculescu S., Ritli L., Baghiu D., Uscatescu V., Petrovanu C., Stancu P., Savescu D., Cucuianu A., Schramm W. Development of inhibitors in haemophilia. Ongoing epidemiological study. Hamostaseologie 2011, 31(Suppl. 1):S20-S23.
138. Benson G., Auerswald G., Elezović I., Lambert T., Ljung R., Morfini M., Remor E., Salek S.Z. Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice. Eur. J. Haematol. 2012, 19. 10.1111/j.1600-0609.2012.01754.x.
139. Russell P., Eley S.M., Hibbs S.E., Manchee R.J., Stagg A.J., Titball R.W. A comparison of plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine 1995, 13:1551-1556.
140. Perry R.D., Fetherston J.D. Yersinia pestis - etiologic agent of plague. Clin. Microbiol. Rev. 1997, 10:35-66.
141. Inglesby T.V., Dennis D.T., Henderson D.A., Bartlett J.G., Ascher M.S., Eitzen E., Fine A.D., Friedlander A.M., Hauer J., Koerner J.F., Layton M., McDade J., Osterholm M.T., O'Toole T., Parker G., Perl T.M., Russell P.K., Schoch-Spana M., Tonat K. Plague as a biological weapon: medical and public health management, Working Group on Civilian Biodefense. JAMA 2000, 283:2281-2290.
142. Titball R.W., Williamson E.D. Vaccination against bubonic and pneumonic plague. Vaccine 2001, 19:4175-4184.
143. http://www.promedmail.org.
144. Alvarez M.L., Cardineau G.A. Prevention of bubonic and pneumonic plague using plant-derived vaccines. Biotechnol. Adv. 2010, 28:184-196.
145. Kingston R., Burke F., Robinson J.H., Bedford P.A., Jones S.M., Knight S.C., Williamson E.D. The fraction 1 and V protein antigens of Yersinia pestis activate dendritic cells to induce primary T cell responses. Clin. Exp. Immunol. 2007, 149:561-569.
146. Santi L., Giritch A., Roy C.J., Marillonnet S., Klimyuk V., Gleba Y., Webb R., Arntzen C.J., Mason H.S. Protection conferred by recombinant Yersinia pestis antigens produced by a rapid and highly scalable plant expression system. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:861-866.
147. Mett V., Lyons J., Musiychuk K., Chichester J.A., Brasil T., Couch R., Sherwood R., Palmer G.A., Streatfield S.J., Yusibov V. A plant-produced plague vaccine candidate confers protection to monkeys. Vaccine 2007, 25:3014-3017.
148. Chichester J.A., Musiychuk K., Mett V., Lyons J., Yusibov V. A single component two-valent LcrV-F1 vaccine protects non-human primates against pneumonic plague. Vaccine 2009, 27:3471-3474.
149. Cholera vaccines. A brief summary of the March 2010 position paper, 2010. http://www.who.int/immunization/Cholera_PP_Accomp_letter_Mar_10_2010.pdf.
150. Sinclair D., Abba K., Zaman K., Qadri F., Graves P.M. Oral vaccines for preventing cholera. Cochrane Database Syst. Rev. 2011, 3:CD008603.
151. Lopez A.L., Clemens J.D., Deen J., Jodar L. Cholera vaccines for the developing world. Hum. Vaccin. 2008, 4:165-169.
152. Is a vaccine available to prevent cholera? 2011, http://www.cdc.gov/cholera/general/#vaccine.
153. Olsson L., Parment P.A. Present and future cholera vaccines. Expert Rev. Vaccines 2006, 5:751-752.
154. Mahalanabis D., Lopez A.L., Sur D., Deen J., Manna B., Kanungo S., von Seidlein L., Carbis R., Han S.H., Shin S.H., Attridge S., Rao R., Holmgren J., Clemens J., Bhattacharya S.K. A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India. PLoS One 2008, 3:e2323.
155. de Haan L., Verweij W., Agsteribbe E., Wilschut J. The role of ADP-ribosylation and GM1-binding activity in the mucosal immunogenicity and adjuvanticity of the Escherichia coli heat-labile enterotoxin and Vibrio cholerae cholera toxin. Immunol. Cell Biol. 1998, 76:270-279.
156. Tsuji T., Watanabe K., Miyama A. Monomer of the B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli has little ability to bind to GM1 ganglioside compared to its coligenoid. Microbiol. Immunol. 1995, 39:817-819.
157. Mastroeni P., Bowe F., Cahill R., Simmons C., Dougan G. Vaccines against gut pathogens. Gut 1999, 45:633-635.
158. Tacket C.O., Mason H.S., Losonsky G., Clements J.D., Levine M.M., Arntzen C.J. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nat. Med. 1998, 4:607-609.
159. Karaman S., Cunnick J., Wang K. Expression of the cholera toxin B subunit (CT-B) in maize seeds and a combined mucosal treatment against cholera and traveler's diarrhea. Plant Cell Rep. 2012, 31:527-537.
160. Nochi T., Yuki Y., Katakai Y., Shibata H., Tokuhara D., Mejima M., Kurokawa S., Takahashi Y., Nakanishi U., Ono F., Mimuro H., Sasakawa C., Takaiwa F., Terao K., Kiyono H. A rice-based oral cholera vaccine induces macaque-specific systemic neutralizing antibodies but does not influence pre-existing intestinal immunity. J. Immunol. 2009, 183:6538-6544.
161. Daniell H., Chebolu S., Kumar S., Singleton M., Falconer R. (2005) Chloroplast-derived vaccine antigens and other therapeutic proteins. Vaccine 2005, 23:1779-1783.
162. Daniell H., Lee S.B., Panchal T., Wiebe P.O. Expression of the native cholera toxin B subunit gene and assembly as functional oligomers in transgenic tobacco chloroplasts. J. Mol. Biol. 2001, 311:1001-1009.
163. Chebolu S., Daniell H. Stable expression of Gal/GalNAc lectin of Entamoeba histolytica in transgenic chloroplasts and immunogenicity in mice towards vaccine development for amoebiasis. Plant Biotechnol. J. 2007, 5:230-239.
164. http://www.who.int/malaria/world_malaria_report_2011/en/.
165. Angov E., Aufiero B.M., Turgeon A.M., Handenhove M.V., Ockenhouse C.F., Kester K.E., Walsh D.S., McBride J.S., Dubois M.C., Cohen J., Haynes J.D., Eckels K.H., Hepper D.G., Ballou W.R., Diggs C.L., Lyon J.A. Development and pre-clinical analysis of a Plasmodium falciparum merozoite surface protein-142 malaria vaccine. Mol. Biochem. Parasitol. 2003, 128:195-204.
166. Malkin E., Dubovsky F., Moree M. Progress towards the development of malaria vaccines. Trends Parasitol. 2006, 22:292-295.
167. Malkin E., Hu J., Li Z., Chen Z., Bi X., Reed Z., Dubovsky F., Liu J., Wang Q., Pan X., Chen T., Giersing B., Xu Y., Kang X., Gu J., Shen Q., Tucker K., Tierney E., Pan W., Long C., Cao Z. A phase 1 trial of PfCP2.9: an AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria. Vaccine 2008, 26:6864-6873.
168. Aide P., Bassat Q., Alonso P.L. Towards an effective malaria vaccine. Arch. Dis. Child. 2007, 92:476-479.
169. Greenwood B.M., Bojang K., Whitty C.J., Targett G.A. Malaria. Lancet 2005, 365:1487-1498.
170. Maher B. Malaria: the end of the beginning. Nature 2008, 451:1042-1046.
171. Good M.F., Kaslow D.C., Miller L.M. Pathways and strategies for developing a malaria blood-stage vaccine. Annu. Rev. Immunol. 1998, 16:57-87.
172. Remarque E.J., Faber B.W., Kocken C.H., Thomas A.W. Apical membrane antigen 1: a malaria vaccine candidate in review. Trends Parasitol. 2008, 24:74-84.
173. Dutta S., Haynes J.D., Moch J.K., Barbosa A., Lanar D.E. Invasion-inhibitory antibodies inhibit proteolytic processing of apical membrane antigen 1 of Plasmodium falciparum merozoites. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:12295-12300.
174. Hodder A.N., Crewther P.E., Anders R.F. Specificity of the Protective Antibody Response to Apical Membrane Antigen 1. Infect. Immun. 2001, 69:3286-3294.
175. Narum D.L., Haynes J.D., Fuhrmann S., Moch K., Liang H., Hoffman S.L., Sim B.K. Antibodies against the Plasmodium falciparum receptor binding domain of EBA-175 block invasion pathways that do not involve sialic acid. Infect. Immun. 2000, 68:1964-1966.
176. Blackman M.J., Heidrich H.G., Donachie S., McBride J.S., Holder A.A. A single fragment of a malaria meroxoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J. Exp. Med. 1990, 172:379-382.
177. Chang S.P., Case S.E., Gosnell W.L., Hashimoto A., Kramer K.J., Tam L.Q., Hashiro C.Q., Nikaido C.M., Gibson H.L., Lee-Ng C.T., Barr P.J., Yokota B.T., Hut G.S. A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 protects Aotus monkeys against malaria. Infect. Immun. 1996, 64:253-261.
178. Darko C.A., Angov E., Collins W.E., Bergmann-Leitner E.S., Girouard A.S., Hitt S.L., McBride J.S., Diggs C.L., Holder A.A., Long C.A., Barnwell J.W., Lyon J.A. The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites. Infect. Immun. 2005, 73:287-297.
179. Egan A.E., Blackman M.J., Kaslow D.C. Vaccine efficacy of recombinant Plasmodium falciparum merozoite surface protein 1 in malaria-naive, -exposed and/or -rechallenged Aotus vociferons monkeys. Infect. Immun. 2000, 68:1418-1427.
180. Tian J.H., Kumar S., Kaslow D.C., Miller L.H. Comparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoelii. Infect. Immun. 1997, 65:3032-3036.
181. Wang L., Webster D.E., Campbell A.E., Dry I.B., Wesselingh S.L., Coppel R.L. Immunogenicity of Plasmodium yoelii merozoite surface protein 4/5 produced in transgenic plants. Int. J. Parasitol. 2008, 38:103-110.
182. Sachdeva S., Mohmmed A., Dasaradhi P.V., Crabb B.S., Katyal A., Malhotra P., Chauhan V.S. Immunogenicity and protective efficacy of Escherichia coli expressed Plasmodium falciparum merozoite surface protein-1(42) using human compatible adjuvants. Vaccine 2006, 24:2007-2016.
183. Ratner M. Pfizer stakes a claim in plant cell-made biopharmaceuticals. Nat. Biotechnol. 2010, 28:107-108.
184. http://oig.hhs.gov/oei/reports/oei-04-10-00430.asp.
185. Holmgren J., Czerkinsky C. Mucosal immunity and vaccines. Nat. Med. 2005, 11:S45-S53.
186. Thompson K.M., Tebbens R.J. Current polio global eradication and control policy options: perspectives from modeling and prerequisites for oral poliovirus vaccine cessation. Expert Rev. Vaccines 2012, 11:449-459.
187. Hird T.R., Grassly N.C. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge. PLoS Pathog. 2012, 8:e1002599. 10.1371/journal.ppat.1002599.
188. Kivity S., Agmon-Levin N., Blank M., Shoenfeld Y. Infections and autoimmunity - friends or foes?. Trends Immunol. 2009, 30:409-414.
189. Steinman L. Immune therapy for autoimmune diseases. Science 2004, 305:212-216.
190. Wang J., Lozie J., Johnson G., Kirshner S., Verthelyi D., Pariser A., Shores E., Rosenberg A. Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat. Biotechnol. 2008, 26:901-908.
191. Nayak S., Sivakumar R., Cao O., Daniell H., Byrne B.J., Herzog R.W. Mapping the T helper cell response to acid α-glucosidase in Pompe mice. Mol. Genet. Metab. 2012, 106:189-195.
192. Jayandharan G.R., Srivastava A. Hemophilia: disease, diagnosis and treatment. J. Genet. Syndr. Gene Ther. 2011, S1:005. 10.4172/2157-7412.S1-005.
193. Cao O., Hoffman B.E., Moghimi B., Nayak S., Cooper M., Zhou S., Ertl H.C.J., High K.A., Herzog R.W. Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B. Mol. Ther. 2009, 17:1733-1742.
194. McKenzie S.J., Halsey J.F. Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. J. Immunol. 1984, 133:1818-1824.
195. Van der Heijden P.J., Bianchi A.T., Dol M., Pals J.W., Stok W., Bokhout B.A. Manipulation of intestinal immune responses against ovalbumin by cholera toxin and its B subunit in mice. Immunology 1991, 72:89-93.
196. Sánchez J., Holmgren J. Cholera toxin - a foe & a friend. Indian J. Med. Res. 2011, 133:153-163.
197. Odumosu O., Payne K., Baez I., Jutzy J., Wall N., Langridge W. Suppression of dendritic cell activation by diabetes autoantigens linked to the cholera toxin B subunit. Immunobiology 2011, 216:447-456.
198. Odumosu O., Nicholas D., Payne K., Langridge W. Cholera toxin B subunit linked to glutamic acid decarboxylase suppresses dendritic cell maturation and function. Vaccine 2011, 29:8451-8458.
199. Stanford M., Whittall T., Bergmeier L.A., Lindblad M., Lundin S., Shinnick T., Mizushima Y., Holmgren J., Lehner T. Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease. Clin. Exp. Immunol. 2004, 137:201-208.
200. Kendall D.M., Riddle M.C., Rosenstock J., Zhuang D., Kim D.D., Fineman M.S., Baron A.D. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005, 28:1083-1091.
201. Eli Lilly (Netherlands) Byetta (exenatide) summary of product characteristics. Electronic Medicines Compendium. Leatherhead: Datapharm (accessed May 2012). http://www.medicines.org.uk/EMC/medicine/19257/SPC/Byetta+5+micrograms+solution+for+injection%2c+prefilled+pen.++Byetta+10+micrograms+solution+for+injection%2c+prefilled+pen./.
202. Wilson J.P. Surface area of the small intestine in man. Gut 1967, 8:618-621.
203. Holmgren J., Lönnroth I., Månsson J., Svennerholm L. Interaction of cholera toxin and membrane GM1 ganglioside of small intestine. Proc. Natl. Acad. Sci. U. S. A. 1975, 72:2520-2524.
204. Fishman P.H., Bradley R.M., Hom B.E., Moss J. Uptake and metabolism of exogenous gangliosides by cultured cells: effect of choleragen on the turnover of GM1. J. Lipid Res. 1983, 24:1002-1011.
205. Wadia J.S., Dowdy S.F. Protein transduction technology. Curr. Opin. Biotechnol. 2002, 13:52-56.
206. Khafagy E.S., Morishita M. Oral biodrug delivery using cell-penetrating peptide. Adv. Drug Deliv. Rev. 2012, 64:531-539.