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Review Article

Augmentation Therapy with Alpha-1 Antitrypsin: Present and Future of Production, Formulation, and Delivery

Author(s): Annalisa Bianchera, Esraa Alomari and Stefano Bruno*

Volume 29, Issue 3, 2022

Published on: 27 December, 2021

Page: [385 - 410] Pages: 26

DOI: 10.2174/0929867328666210525161942

Price: $65

Abstract

Alpha 1-antitrypsin is one of the first protein therapeutics introduced on the market more than 30 years ago, and to date, it is indicated only for the treatment of the severe forms of a genetic condition known as alpha-1 antitrypsin deficiency. The only approved preparations are derived from plasma, posing potential problems associated with its limited supply and high processing costs. Moreover, augmentation therapy with alpha-1 antitrypsin is still limited to intravenous infusions, a cumbersome regimen for patients. Here, we review the recent literature on its possible future developments, focusing on i) the recombinant alternatives to the plasma-derived protein, ii) novel formulations, and iii) novel administration routes. Regulatory issues and the still unclear noncanonical functions of alpha-1 antitrypsin, possibly associated with the glycosylation pattern found only in the plasma-derived protein, have hindered the introduction of new products. However, potentially new therapeutic indications other than the treatment of alpha-1 antitrypsin deficiency might open the way to new sources and new formulations.

Keywords: Alpha 1-antitrypsin, alpha 1-proteinase inhibitor, neutrophil elastase, augmentation therapy, protein therapeutics formulation, pulmonary drug delivery

« Previous Next »
[1]
Janciauskiene, S.M.; Bals, R.; Koczulla, R.; Vogelmeier, C.; Köhnlein, T.; Welte, T. The discovery of α1-antitrypsin and its role in health and disease. Respir. Med., 2011, 105(8), 1129-1139.
[http://dx.doi.org/10.1016/j.rmed.2011.02.002] [PMID: 21367592]
[2]
Winkler, I.G.; Hendy, J.; Coughlin, P.; Horvath, A.; Lévesque, J.P. Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization. J. Exp. Med., 2005, 201(7), 1077-1088.
[http://dx.doi.org/10.1084/jem.20042299] [PMID: 15795238]
[3]
Pham, C.T. Neutrophil serine proteases: specific regulators of inflammation. Nat. Rev. Immunol., 2006, 6(7), 541-550.
[http://dx.doi.org/10.1038/nri1841] [PMID: 16799473]
[4]
Janciauskiene, S.; Wrenger, S.; Immenschuh, S.; Olejnicka, B.; Greulich, T.; Welte, T.; Chorostowska-Wynimko, J. The multifaceted effects of alpha1-antitrypsin on neutrophil functions. Front. Pharmacol., 2018, 9, 341.
[http://dx.doi.org/10.3389/fphar.2018.00341] [PMID: 29719508]
[5]
Afonina, I.S.; Müller, C.; Martin, S.J.; Beyaert, R. Proteolytic processing of interleukin-1 family cytokines: variations on a common theme. Immunity, 2015, 42(6), 991-1004.
[http://dx.doi.org/10.1016/j.immuni.2015.06.003] [PMID: 26084020]
[6]
Lockett, A.D.; Kimani, S.; Ddungu, G.; Wrenger, S.; Tuder, R.M.; Janciauskiene, S.M.; Petrache, I. α1-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-α. Am. J. Respir. Cell Mol. Biol., 2013, 49(1), 143-150.
[http://dx.doi.org/10.1165/rcmb.2012-0515OC] [PMID: 23526215]
[7]
Sohrab, S.; Petrusca, D.N.; Lockett, A.D.; Schweitzer, K.S.; Rush, N.I.; Gu, Y.; Kamocki, K.; Garrison, J.; Petrache, I. Mechanism of alpha-1 antitrypsin endocytosis by lung endothelium. FASEB J., 2009, 23(9), 3149-3158.
[http://dx.doi.org/10.1096/fj.09-129304] [PMID: 19423638]
[8]
Janciauskiene, S.; Larsson, S.; Larsson, P.; Virtala, R.; Jansson, L.; Stevens, T. Inhibition of lipopolysaccharide-mediated human monocyte activation, in vitro, by alpha1-antitrypsin. Biochem. Biophys. Res. Commun., 2004, 321(3), 592-600.
[http://dx.doi.org/10.1016/j.bbrc.2004.06.123] [PMID: 15358147]
[9]
Petrache, I.; Fijalkowska, I.; Medler, T.R.; Skirball, J.; Cruz, P.; Zhen, L.; Petrache, H.I.; Flotte, T.R.; Tuder, R.M. alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis. Am. J. Pathol., 2006, 169(4), 1155-1166.
[http://dx.doi.org/10.2353/ajpath.2006.060058] [PMID: 17003475]
[10]
Bucurenci, N.; Blake, D.R.; Chidwick, K.; Winyard, P.G. Inhibition of neutrophil superoxide production by human plasma alpha 1-antitrypsin. FEBS Lett., 1992, 300(1), 21-24.
[http://dx.doi.org/10.1016/0014-5793(92)80156-B] [PMID: 1312485]
[11]
Schwarz, N.; Tumpara, S.; Wrenger, S.; Ercetin, E.; Hamacher, J.; Welte, T.; Janciauskiene, S. Alpha1-antitrypsin protects lung cancer cells from staurosporine-induced apoptosis: the role of bacterial lipopolysaccharide. Sci. Rep., 2020, 10(1), 9563.
[http://dx.doi.org/10.1038/s41598-020-66825-w] [PMID: 32533048]
[12]
Nita, I.; Hollander, C.; Westin, U.; Janciauskiene, S.M. Prolastin, a pharmaceutical preparation of purified human alpha1-antitrypsin, blocks endotoxin-mediated cytokine release. Respir. Res., 2005, 6, 12.
[http://dx.doi.org/10.1186/1465-9921-6-12] [PMID: 15683545]
[13]
Lior, Y.; Zaretsky, M.; Ochayon, D.E.; Lotysh, D.; Baranovski, B.M.; Schuster, R.; Guttman, O.; Aharoni, A.; Lewis, E.C. Point mutation of a non-elastase-binding site in human α1-antitrypsin alters its anti-inflammatory properties. Front. Immunol., 2018, 9, 759.
[http://dx.doi.org/10.3389/fimmu.2018.00759] [PMID: 29780379]
[14]
Chandrasekhar, K.; Ke, H.; Wang, N.; Goodwin, T.; Gierasch, L.M.; Gershenson, A.; Hebert, D.N. Cellular folding pathway of a metastable serpin. Proc. Natl. Acad. Sci. USA, 2016, 113(23), 6484-6489.
[http://dx.doi.org/10.1073/pnas.1603386113] [PMID: 27222580]
[15]
Huntington, J.A.; Read, R.J.; Carrell, R.W. Structure of a serpin-protease complex shows inhibition by deformation. Nature, 2000, 407(6806), 923-926.
[http://dx.doi.org/10.1038/35038119] [PMID: 11057674]
[16]
Whisstock, J.C.; Bottomley, S.P. Molecular gymnastics: serpin structure, folding and misfolding. Curr. Opin. Struct. Biol., 2006, 16(6), 761-768.
[http://dx.doi.org/10.1016/j.sbi.2006.10.005] [PMID: 17079131]
[17]
Tsutsui, Y.; Dela Cruz, R.; Wintrode, P.L. Folding mechanism of the metastable serpin α1-antitrypsin. Proc. Natl. Acad. Sci. USA, 2012, 109(12), 4467-4472.
[http://dx.doi.org/10.1073/pnas.1109125109] [PMID: 22392975]
[18]
Kolarich, D.; Weber, A.; Turecek, P.L.; Schwarz, H.P.; Altmann, F. Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms. Proteomics, 2006, 6(11), 3369-3380.
[http://dx.doi.org/10.1002/pmic.200500751] [PMID: 16622833]
[19]
McCarthy, C.; Saldova, R.; Wormald, M.R.; Rudd, P.M.; McElvaney, N.G.; Reeves, E.P. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions. J. Proteome Res., 2014, 13(7), 3131-3143.
[http://dx.doi.org/10.1021/pr500146y] [PMID: 24892502]
[20]
Yin, H.; An, M.; So, P.K.; Wong, M.Y.; Lubman, D.M.; Yao, Z. The analysis of alpha-1-antitrypsin glycosylation with direct LC-MS/MS. Electrophoresis, 2018, 39(18), 2351-2361.
[http://dx.doi.org/10.1002/elps.201700426] [PMID: 29405331]
[21]
Hennen, E.; Czopka, T.; Faissner, A. Structurally distinct LewisX glycans distinguish subpopulations of neural stem/progenitor cells. J. Biol. Chem., 2011, 286(18), 16321-16331.
[http://dx.doi.org/10.1074/jbc.M110.201095] [PMID: 21385876]
[22]
Chiu, M.H.; Tamura, T.; Wadhwa, M.S.; Rice, K.G. in vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues. J. Biol. Chem., 1994, 269(23), 16195-16202.
[http://dx.doi.org/10.1016/S0021-9258(17)33992-3] [PMID: 8206921]
[23]
Chung, H.S.; Kim, J.S.; Lee, S.M.; Park, S.J. Additional N-glycosylation in the N-terminal region of recombinant human alpha-1 antitrypsin enhances the circulatory half-life in Sprague-Dawley rats. Glycoconj. J., 2016, 33(2), 201-208.
[http://dx.doi.org/10.1007/s10719-016-9657-3] [PMID: 26947874]
[24]
Lomas, D.A.; Parfrey, H. Alpha1-antitrypsin deficiency. 4: molecular pathophysiology. Thorax, 2004, 59(6), 529-535.
[http://dx.doi.org/10.1136/thx.2003.006528] [PMID: 15170041]
[25]
Sarkar, A.; Wintrode, P.L. Effects of glycosylation on the stability and flexibility of a metastable protein: the human serpin α(1)-antitrypsin. Int. J. Mass Spectrom., 2011, 302(1-3), 69-75.
[http://dx.doi.org/10.1016/j.ijms.2010.08.003] [PMID: 21765645]
[26]
Kwon, K.S.; Yu, M.H. Effect of glycosylation on the stability of alpha1-antitrypsin toward urea denaturation and thermal deactivation. Biochim. Biophys. Acta, 1997, 1335(3), 265-272.
[http://dx.doi.org/10.1016/S0304-4165(96)00143-2] [PMID: 9202189]
[27]
Stoller, J.K.; Aboussouan, L.S. A review of α1-antitrypsin deficiency. Am. J. Respir. Crit. Care Med., 2012, 185(3), 246-259.
[http://dx.doi.org/10.1164/rccm.201108-1428CI] [PMID: 21960536]
[28]
Hazari, Y.M.; Bashir, A.; Habib, M.; Bashir, S.; Habib, H.; Qasim, M.A.; Shah, N.N.; Haq, E.; Teckman, J.; Fazili, K.M. Alpha-1-antitrypsin deficiency: genetic variations, clinical manifestations and therapeutic interventions. Mutat. Res., 2017, 773, 14-25.
[http://dx.doi.org/10.1016/j.mrrev.2017.03.001] [PMID: 28927525]
[29]
Dunlea, D.M.; Fee, L.T.; McEnery, T.; McElvaney, N.G.; Reeves, E.P. The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals. J. Inflamm. Res., 2018, 11, 123-134.
[http://dx.doi.org/10.2147/JIR.S156405] [PMID: 29618937]
[30]
Hoenderdos, K.; Condliffe, A. The neutrophil in chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol., 2013, 48(5), 531-539.
[http://dx.doi.org/10.1165/rcmb.2012-0492TR] [PMID: 23328639]
[31]
de Serres, F.; Blanco, I. Role of alpha-1 antitrypsin in human health and disease. J. Intern. Med., 2014, 276(4), 311-335.
[http://dx.doi.org/10.1111/joim.12239] [PMID: 24661570]
[32]
Greene, C.M.; Marciniak, S.J.; Teckman, J.; Ferrarotti, I.; Brantly, M.L.; Lomas, D.A.; Stoller, J.K.; McElvaney, N.G. α1-Antitrypsin deficiency. Nat. Rev. Dis. Primers, 2016, 2, 16051.
[http://dx.doi.org/10.1038/nrdp.2016.51] [PMID: 27465791]
[33]
Fairbanks, K.D.; Tavill, A.S. Liver disease in alpha 1-antitrypsin deficiency: a review. Am. J. Gastroenterol., 2008, 103(8), 2136-2141.
[http://dx.doi.org/10.1111/j.1572-0241.2008.01955.x] [PMID: 18796107]
[34]
Tubío-Pérez, R.A.; Torres-Durán, M.; Fernández-Villar, A.; Ruano-Raviña, A. Alpha-1 antitrypsin deficiency and risk of lung cancer: a systematic review. Transl. Oncol., 2021, 14(1)100914
[http://dx.doi.org/10.1016/j.tranon.2020.100914] [PMID: 33142121]
[35]
Huang, X.; Zheng, Y.; Zhang, F.; Wei, Z.; Wang, Y.; Carrell, R.W.; Read, R.J.; Chen, G.Q.; Zhou, A. Molecular mechanism of Z α1-antitrypsin deficiency. J. Biol. Chem., 2016, 291(30), 15674-15686.
[http://dx.doi.org/10.1074/jbc.M116.727826] [PMID: 27246852]
[36]
Lomas, D.A.; Evans, D.L.; Finch, J.T.; Carrell, R.W. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature, 1992, 357(6379), 605-607.
[http://dx.doi.org/10.1038/357605a0] [PMID: 1608473]
[37]
Elliott, P.R.; Stein, P.E.; Bilton, D.; Carrell, R.W.; Lomas, D.A. Structural explanation for the deficiency of S alpha 1-antitrypsin. Nat. Struct. Biol., 1996, 3(11), 910-911.
[http://dx.doi.org/10.1038/nsb1196-910] [PMID: 8901864]
[38]
Renoux, C.; Odou, M.F.; Tosato, G.; Teoli, J.; Abbou, N.; Lombard, C.; Zerimech, F.; Porchet, N.; Chapuis Cellier, C.; Balduyck, M.; Joly, P. Description of 22 new alpha-1 antitrypsin genetic variants. Orphanet J. Rare Dis., 2018, 13(1), 161.
[http://dx.doi.org/10.1186/s13023-018-0897-0] [PMID: 30223862]
[39]
Hernández-Pérez, J.M.; Ramos-Díaz, R.; Pérez, J.A. Identification of a new defective SERPINA1 allele (PI*Zla palma) encoding an alpha-1-antitrypsin with altered glycosylation pattern. Respir. Med., 2017, 131, 114-117.
[http://dx.doi.org/10.1016/j.rmed.2017.08.015] [PMID: 28947017]
[40]
McCarthy, C.; Saldova, R.; O’Brien, M.E.; Bergin, D.A.; Carroll, T.P.; Keenan, J.; Meleady, P.; Henry, M.; Clynes, M.; Rudd, P.M.; Reeves, E.P.; McElvaney, N.G. Increased outer arm and core fucose residues on the N-glycans of mutated alpha-1 antitrypsin protein from alpha-1 antitrypsin deficient individuals. J. Proteome Res., 2014, 13(2), 596-605.
[http://dx.doi.org/10.1021/pr400752t] [PMID: 24328305]
[41]
Gadek, J.E.; Klein, H.G.; Holland, P.V.; Crystal, R.G. Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J. Clin. Invest., 1981, 68(5), 1158-1165.
[http://dx.doi.org/10.1172/JCI110360] [PMID: 7028785]
[42]
Teschler, H. Long-term experience in the treatment of alpha1-antitrypsin deficiency: 25 years of augmentation therapy. Eur. Respir. Rev., 2015, 24(135), 46-51.
[http://dx.doi.org/10.1183/09059180.10010714] [PMID: 25726554]
[43]
Chapman, K.R.; Stockley, R.A.; Dawkins, C.; Wilkes, M.M.; Navickis, R.J. Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis. COPD, 2009, 6(3), 177-184.
[http://dx.doi.org/10.1080/15412550902905961] [PMID: 19811373]
[44]
Chapman, K.R.; Burdon, J.G.; Piitulainen, E.; Sandhaus, R.A.; Seersholm, N.; Stocks, J.M.; Stoel, B.C.; Huang, L.; Yao, Z.; Edelman, J.M.; McElvaney, N.G.; Group, R.T.S. RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): A randomised, double-blind, placebo-controlled trial. Lancet, 2015, 386(9991), 360-368.
[http://dx.doi.org/10.1016/S0140-6736(15)60860-1] [PMID: 26026936]
[45]
McElvaney, N.G.; Burdon, J.; Holmes, M.; Glanville, A.; Wark, P.A.; Thompson, P.J.; Hernandez, P.; Chlumsky, J.; Teschler, H.; Ficker, J.H.; Seersholm, N.; Altraja, A.; Mäkitaro, R.; Chorostowska-Wynimko, J.; Sanak, M.; Stoicescu, P.I.; Piitulainen, E.; Vit, O.; Wencker, M.; Tortorici, M.A.; Fries, M.; Edelman, J.M.; Chapman, K.R.; Group, R.E.T. RAPID Extension Trial Group. Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir. Med., 2017, 5(1), 51-60.
[http://dx.doi.org/10.1016/S2213-2600(16)30430-1] [PMID: 27916480]
[46]
Ma, S.; Lin, Y.Y.; Cantor, J.O.; Chapman, K.R.; Sandhaus, R.A.; Fries, M.; Edelman, J.M.; McElvaney, G.; Turino, G.M. The effect of alpha-1 proteinase inhibitor on biomarkers of elastin degradation in alpha-1 antitrypsin deficiency: an analysis of the RAPID/RAPID extension trials. Chronic Obstr. Pulm. Dis. (Miami), 2016, 4(1), 34-44.
[http://dx.doi.org/10.15326/jcopdf.4.1.2016.0156] [PMID: 28848909]
[47]
Smith, D.J.; Ellis, P.R.; Turner, A.M. Exacerbations of Lung Disease in Alpha-1 Antitrypsin Deficiency. Chronic Obstr. Pulm. Dis. (Miami), 2020, 8(1), 162-176.
[http://dx.doi.org/10.15326/jcopdf.2020.0173] [PMID: 33238089]
[48]
Wanner, A. Alpha-1 antitrypsin as a therapeutic agent for conditions not associated with alpha-1 antitrypsin deficiency.Alpha-1 Antitrypsin; Wanner, A.; Sandhaus, R., Eds.; Humana Press: Cham, 2016, pp. 141-155.
[http://dx.doi.org/10.1007/978-3-319-23449-6_8]
[49]
Kim, M.; Cai, Q.; Oh, Y. Therapeutic potential of alpha-1 antitrypsin in human disease. Ann. Pediatr. Endocrinol. Metab., 2018, 23(3), 131-135.
[http://dx.doi.org/10.6065/apem.2018.23.3.131] [PMID: 30286568]
[50]
Wanner, A. COPD: new lessons from alpha1-antitrypsin deficiency? Chest, 2009, 135(5), 1342-1344.
[http://dx.doi.org/10.1378/chest.08-2341] [PMID: 19420201]
[51]
Lo Bello, F.; Hansbro, P.M.; Donovan, C.; Coppolino, I.; Mumby, S.; Adcock, I.M.; Caramori, G. New drugs under development for COPD. Expert Opin. Emerg. Drugs, 2020, 25(4), 419-431.
[http://dx.doi.org/10.1080/14728214.2020.1819982] [PMID: 32882146]
[52]
McElvaney, N.G. Alpha-1 antitrypsin therapy in cystic fibrosis and the lung disease associated with alpha-1 antitrypsin deficiency. Ann. Am. Thorac. Soc., 2016, 13(Suppl. 2), S191-S196.
[http://dx.doi.org/10.1513/annalsats.201504-245kv] [PMID: 27115956]
[53]
Gaggar, A.; Chen, J.; Chmiel, J.F.; Dorkin, H.L.; Flume, P.A.; Griffin, R.; Nichols, D.; Donaldson, S.H. Inhaled alpha1-proteinase inhibitor therapy in patients with cystic fibrosis. J. Cyst. Fibros., 2016, 15(2), 227-233.
[http://dx.doi.org/10.1016/j.jcf.2015.07.009] [PMID: 26321218]
[54]
Berger, M.; Liu, M.; Uknis, M.E.; Koulmanda, M. Alpha-1-antitrypsin in cell and organ transplantation. Am. J. Transplant., 2018, 18(7), 1589-1595.
[http://dx.doi.org/10.1111/ajt.14756] [PMID: 29607607]
[55]
Tawara, I.; Sun, Y.; Lewis, E.C.; Toubai, T.; Evers, R.; Nieves, E.; Azam, T.; Dinarello, C.A.; Reddy, P. Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation. Proc. Natl. Acad. Sci. USA, 2012, 109(2), 564-569.
[http://dx.doi.org/10.1073/pnas.1117665109] [PMID: 22203983]
[56]
Magenau, J.M.; Goldstein, S.C.; Peltier, D.; Soiffer, R.J.; Braun, T.; Pawarode, A.; Riwes, M.M.; Kennel, M.; Antin, J.H.; Cutler, C.S.; Ho, V.T.; Alyea, E.P., III; Parkin, B.L.; Yanik, G.A.; Choi, S.W.; Lewis, E.C.; Dinarello, C.A.; Koreth, J.; Reddy, P. α1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood, 2018, 131(12), 1372-1379.
[http://dx.doi.org/10.1182/blood-2017-11-815746] [PMID: 29437593]
[57]
Giannoni, L.; Morin, F.; Robin, M.; Peyneau, M.; Schlageter, M.H.; Desmier, D.; Pagliuca, S.; Sutra Del Galy, A.; Sicre de Fontbrune, F.; Xhaard, A.; Dhedin, N.; Moins-Teisserenc, H.; Peffault de Latour, R.; Socie, G.; Michonneau, D. Human-Derived alpha1-Antitrypsin is Still Efficacious in Heavily Pretreated Patients with Steroid-Resistant Gastrointestinal Graft-versus-Host Disease. Biol. Blood Marrow Transplant., 2020, 26(9), 1620-1626.
[http://dx.doi.org/10.1016/j.bbmt.2020.05.014] [PMID: 32454215]
[58]
Koulmanda, M.; Bhasin, M.; Fan, Z.; Hanidziar, D.; Goel, N.; Putheti, P.; Movahedi, B.; Libermann, T.A.; Strom, T.B. Alpha 1-antitrypsin reduces inflammation and enhances mouse pancreatic islet transplant survival. Proc. Natl. Acad. Sci. USA, 2012, 109(38), 15443-15448.
[http://dx.doi.org/10.1073/pnas.1018366109] [PMID: 22949661]
[59]
Wang, J.; Sun, Z.; Gou, W.; Adams, D.B.; Cui, W.; Morgan, K.A.; Strange, C.; Wang, H. α-1 antitrypsin enhances islet engraftment by suppression of instant blood-mediated inflammatory reaction. Diabetes, 2017, 66(4), 970-980.
[http://dx.doi.org/10.2337/db16-1036] [PMID: 28069642]
[60]
Lin, H.; Chen, M.; Tian, F.; Tikkanen, J.; Ding, L.; Andrew Cheung, H.Y.; Nakajima, D.; Wang, Z.; Mariscal, A.; Hwang, D.; Cypel, M.; Keshavjee, S.; Liu, M. alpha1-Anti-trypsin improves function of porcine donor lungs during ex-vivo lung perfusion. J. Heart Lung Transplant., 2018, 37(5), 656-666.
[http://dx.doi.org/10.1016/j.healun.2017.09.019] [PMID: 29153638]
[61]
Emtiazjoo, A.M.; Hu, H.; Lu, L.; Brantly, M.L. Alpha-1 antitrypsin attenuates acute lung allograft injury in a rat lung transplant model. Transplant. Direct, 2019, 5(6)e458
[http://dx.doi.org/10.1097/TXD.0000000000000898] [PMID: 31723592]
[62]
Koulmanda, M.; Bhasin, M.; Hoffman, L.; Fan, Z.; Qipo, A.; Shi, H.; Bonner-Weir, S.; Putheti, P.; Degauque, N.; Libermann, T.A.; Auchincloss, H., Jr; Flier, J.S.; Strom, T.B. Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice. Proc. Natl. Acad. Sci. USA, 2008, 105(42), 16242-16247.
[http://dx.doi.org/10.1073/pnas.0808031105] [PMID: 18852471]
[63]
Weir, G.C.; Ehlers, M.R.; Harris, K.M.; Kanaparthi, S.; Long, A.; Phippard, D.; Weiner, L.J.; Jepson, B.; McNamara, J.G.; Koulmanda, M.; Strom, T.B.; Team, I.R.S. ITN RETAIN Study Team. Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase I clinical trial (RETAIN) to assess safety and pharmacokinetics. Pediatr. Diabetes, 2018, 19(5), 945-954.
[http://dx.doi.org/10.1111/pedi.12660] [PMID: 29473705]
[64]
Potilinski, M.C.; Ortíz, G.A.; Salica, J.P.; López, E.S.; Fernández Acquier, M.; Chuluyan, E.; Gallo, J.E. Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy. PLoS One, 2020, 15(2)e0228895
[http://dx.doi.org/10.1371/journal.pone.0228895] [PMID: 32032388]
[65]
Ortiz, G.; Lopez, E.S.; Salica, J.P.; Potilinski, C.; Fernández Acquier, M.; Chuluyan, E.; Gallo, J.E. Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina. Exp. Eye Res., 2018, 174, 29-39.
[http://dx.doi.org/10.1016/j.exer.2018.05.013] [PMID: 29778740]
[66]
Ortiz, G.; Salica, J.P.; Chuluyan, E.H.; Gallo, J.E. Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option? Biol. Res., 2014, 47, 58.
[http://dx.doi.org/10.1186/0717-6287-47-58] [PMID: 25723058]
[67]
Song, S. Alpha-1 antitrypsin therapy for autoimmune disorders. Chronic Obstr. Pulm. Dis. (Miami), 2018, 5(4), 289-301.
[http://dx.doi.org/10.15326/jcopdf.5.4.2018.0131] [PMID: 30723786]
[68]
Jeong, K.H.; Lim, J.H.; Lee, K.H.; Kim, M.J.; Jung, H.Y.; Choi, J.Y.; Cho, J.H.; Park, S.H.; Kim, Y.L.; Kim, C.D. Protective effect of alpha 1-antitrypsin on renal ischemia-reperfusion injury. Transplant. Proc., 2019, 51(8), 2814-2822.
[http://dx.doi.org/10.1016/j.transproceed.2019.04.084] [PMID: 31439327]
[69]
Toldo, S.; Seropian, I.M.; Mezzaroma, E.; Van Tassell, B.W.; Salloum, F.N.; Lewis, E.C.; Voelkel, N.; Dinarello, C.A.; Abbate, A. Alpha-1 antitrypsin inhibits caspase-1 and protects from acute myocardial ischemia-reperfusion injury. J. Mol. Cell. Cardiol., 2011, 51(2), 244-251.
[http://dx.doi.org/10.1016/j.yjmcc.2011.05.003] [PMID: 21600901]
[70]
Abouzaki, N.A.; Christopher, S.; Trankle, C.; Van Tassell, B.W.; Carbone, S.; Mauro, A.G.; Buckley, L.; Toldo, S.; Abbate, A. Inhibiting the inflammatory injury after myocardial ischemia reperfusion with plasma-derived alpha-1 antitrypsin: a post Hoc analysis of the VCU-α1RT study. J. Cardiovasc. Pharmacol., 2018, 71(6), 375-379.
[http://dx.doi.org/10.1097/FJC.0000000000000583] [PMID: 29634656]
[71]
Heurich, A.; Hofmann-Winkler, H.; Gierer, S.; Liepold, T.; Jahn, O.; Pöhlmann, S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J. Virol., 2014, 88(2), 1293-1307.
[http://dx.doi.org/10.1128/JVI.02202-13] [PMID: 24227843]
[72]
Oguntuyo, K. Y.; Stevens, C. S.; Siddiquey, M. N.; Schilke, R. M.; Woolard, M. D.; Zhang, H.; Acklin, J. A.; Ikegame, S.; Hung, C. T.; Lim, J. K.; Cross, R. W.; Geisbert, T. W.; Ivanov, S. S.; Kamil, J. P.; Lee, B. In plain sight: The role of alpha-1-antitrypsin in COVID-19 pathogenesis and therapeutics. BioRxiv, 2020, preprint, 2020.08.14.248880.,
[http://dx.doi.org/10.1101/2020.08.14.248880] [PMID: 32817940]
[73]
McElvaney, O.J.; McEvoy, N.L.; McElvaney, O.F.; Carroll, T.P.; Murphy, M.P.; Dunlea, D.M.; Ní Choileáin, O.; Clarke, J.; O’Connor, E.; Hogan, G.; Ryan, D.; Sulaiman, I.; Gunaratnam, C.; Branagan, P.; O’Brien, M.E.; Morgan, R.K.; Costello, R.W.; Hurley, K.; Walsh, S.; de Barra, E.; McNally, C.; McConkey, S.; Boland, F.; Galvin, S.; Kiernan, F.; O’Rourke, J.; Dwyer, R.; Power, M.; Geoghegan, P.; Larkin, C.; O’Leary, R.A.; Freeman, J.; Gaffney, A.; Marsh, B.; Curley, G.F.; McElvaney, N.G. Characterization of the inflammatory response to severe COVID-19 Illness. Am. J. Respir. Crit. Care Med., 2020, 202(6), 812-821.
[http://dx.doi.org/10.1164/rccm.202005-1583OC] [PMID: 32584597]
[74]
Azouz, N. P.; Klingler, A. M.; Callahan, V.; Akhrymuk, I. V.; Elez, K.; Raich, L.; Henry, B. M.; Benoit, J. L.; Benoit, S. W.; Noe, F.; Kehn-Hall, K.; Rothenberg, M. E. Alpha 1 antitrypsin is an inhibitor of the SARS-CoV-2-priming protease TMPRSS2. BioRxiv., 2020, 2020.05.04.077826.,
[http://dx.doi.org/10.1101/2020.05.04.077826 ] [PMID: 33052338]
[75]
Bai, X.; Hippensteel, J.; Leavitt, A.; Maloney, J.P.; Beckham, D.; Garcia, C.; Li, Q.; Freed, B.M.; Ordway, D.; Sandhaus, R.A.; Chan, E.D. Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19. Med. Hypotheses, 2021, 146110394
[http://dx.doi.org/10.1016/j.mehy.2020.110394] [PMID: 33239231]
[76]
Duthie, E.S.; Lorenz, L. Protease inhibitors. 1. Assay and nature of serum antiprotease. Biochem. J., 1949, 44(2), 167-173.
[http://dx.doi.org/10.1042/bj0440167] [PMID: 16748493]
[77]
Viglio, S.; Iadarola, P.; D’Amato, M.; Stolk, J. Methods of purification and application procedures of alpha1 antitrypsin: a long-lasting history. Molecules, 2020, 25(17)E4014
[http://dx.doi.org/10.3390/molecules25174014] [PMID: 32887469]
[78]
Zheng, B.N.; Ding, C.H.; Chen, S.J.; Zhu, K.; Shao, J.; Feng, J.; Xu, W.P.; Cai, L.Y.; Zhu, C.P.; Duan, W.; Ding, J.; Zhang, X.; Luo, C.; Xie, W.F. Targeting PRMT5 activity inhibits the malignancy of hepatocellular carcinoma by promoting the transcription of HNF4α. Theranostics, 2019, 9(9), 2606-2617.
[http://dx.doi.org/10.7150/thno.32344] [PMID: 31131056]
[79]
Huangfu, C.; Zhang, J.; Ma, Y.; Jia, J.; Lv, M.; Zhao, X.; Zhang, J. New process for purifying high purity α1-antitrypsin from Cohn Fraction IV by chromatography: a promising method for the better utilization of plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1046, 156-164.
[http://dx.doi.org/10.1016/j.jchromb.2017.01.044] [PMID: 28183045]
[80]
Kee, S.; Weber, D.; Popp, B.; Nowak, T.; Schafer, W.; Groner, A.; Roth, N.J. Pathogen safety and characterisation of a highly purified human alpha1-proteinase inhibitor preparation. Biologicals, 2017, 47, 25-32.
[http://dx.doi.org/10.1016/j.biologicals.2017.03.003] [PMID: 28377078]
[81]
Matthiessen, H.P.; Willemse, J.; Weber, A.; Turecek, P.L.; Deiteren, K.; Hendriks, D.; Ehrlich, H.J.; Schwarz, H.P. Ethanol dependence of alpha 1-antitrypsin C-terminal Lys truncation mediated by basic carboxypeptidases. Transfusion, 2008, 48(2), 314-320.
[http://dx.doi.org/10.1111/j.1537-2995.2007.01525.x] [PMID: 18028276]
[82]
Boerema, D.J.; An, B.; Gandhi, R.P.; Papineau, R.; Regnier, E.; Wilder, A.; Molitor, A.; Tang, A.P.; Kee, S.M. Biochemical comparison of four commercially available human alpha1-proteinase inhibitors for treatment of alpha1-antitrypsin deficiency. Biologicals, 2017, 50, 63-72.
[http://dx.doi.org/10.1016/j.biologicals.2017.08.010] [PMID: 28882403]
[83]
Ruhaak, L.R.; Koeleman, C.A.; Uh, H.W.; Stam, J.C.; van Heemst, D.; Maier, A.B.; Houwing-Duistermaat, J.J.; Hensbergen, P.J.; Slagboom, P.E.; Deelder, A.M.; Wuhrer, M. Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A. PLoS One, 2013, 8(9)e73082
[http://dx.doi.org/10.1371/journal.pone.0073082] [PMID: 24039863]
[84]
Karnaukhova, E.; Ophir, Y.; Golding, B. Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use. Amino Acids, 2006, 30(4), 317-332.
[http://dx.doi.org/10.1007/s00726-005-0324-4] [PMID: 16773239]
[85]
Lusch, A.; Kaup, M.; Marx, U.; Tauber, R.; Blanchard, V.; Berger, M. Development and analysis of alpha 1-antitrypsin neoglycoproteins: the impact of additional N-glycosylation sites on serum half-life. Mol. Pharm., 2013, 10(7), 2616-2629.
[http://dx.doi.org/10.1021/mp400043r] [PMID: 23668542]
[86]
Cantin, A.M.; Woods, D.E.; Cloutier, D.; Dufour, E.K.; Leduc, R. Polyethylene glycol conjugation at Cys232 prolongs the half-life of alpha1 proteinase inhibitor. Am. J. Respir. Cell Mol. Biol., 2002, 27(6), 659-665.
[http://dx.doi.org/10.1165/rcmb.4866] [PMID: 12444025]
[87]
EMA,Guideline on similar biological medicinal products.Available at:, https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-first-version_en.pdf (accessed on 25th December 2021)
[88]
EMA, Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues.Available at: , https://www.ema. europa.eu/en/similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active-substance# document-]history--- revision-1-(current-version)-section (accessed on 25th December 2021)
[89]
EMA Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues., https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active_en-2.pdf(accessed on 25th December 2021)
[90]
FDA Quality considerations in demonstrating biosimilarity to a reference protein product.Available at:, https://www. fda.gov/regulatory-information/search-fda-guidance-docu-ments/quality-considerations-demonstrating-biosimilarity-therapeutic-protein-product-reference-product(accessed on 25th December 2021)
[91]
FDA Scientific considerations in demonstrating biosimilarity to a reference product.Available at: , https://www.fda. gov/regulatory-information/search-fda-guidance-documents/scientific-considerations-demonstrating-biosimilarityreference- product (accessed on 25th December 2021)
[92]
FDA, Questions and Answers on Biosimilar Development and the BPCI Act Guidance for Industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/questions-and-answers-biosimilar-development-and-bpci-act-guidance-industry(accessed on 25th December 2021)
[93]
Wang, J.; Chow, S.C. On the regulatory approval pathway of biosimilar products. Pharmaceuticals (Basel), 2012, 5(4), 353-368.
[http://dx.doi.org/10.3390/ph5040353] [PMID: 24281406]
[94]
Minghetti, P.; Rocco, P.; Cilurzo, F.; Vecchio, L.D.; Locatelli, F. The regulatory framework of biosimilars in the European Union. Drug Discov. Today, 2012, 17(1-2), 63-70.
[http://dx.doi.org/10.1016/j.drudis.2011.08.001] [PMID: 21856438]
[95]
Daller, J. Biosimilars: a consideration of the regulations in the United States and European union. Regul. Toxicol. Pharmacol., 2016, 76, 199-208.
[http://dx.doi.org/10.1016/j.yrtph.2015.12.013] [PMID: 26732800]
[96]
McNulty, M.J.; Silberstein, D.Z.; Kuhn, B.T.; Padgett, H.S.; Nandi, S.; McDonald, K.A.; Cross, C.E. Alpha-1 antitrypsin deficiency and recombinant protein sources with focus on plant sources: updates, challenges and perspectives. Free Radic. Biol. Med., 2020, 163, 10-30.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.030] [PMID: 33279618]
[97]
Huang, C.J.; Lin, H.; Yang, X. Industrial production of recombinant therapeutics in Escherichia coli and its recent advancements. J. Ind. Microbiol. Biotechnol., 2012, 39(3), 383-399.
[http://dx.doi.org/10.1007/s10295-011-1082-9] [PMID: 22252444]
[98]
Valderrama-Rincon, J.D.; Fisher, A.C.; Merritt, J.H.; Fan, Y.Y.; Reading, C.A.; Chhiba, K.; Heiss, C.; Azadi, P.; Aebi, M.; DeLisa, M.P. An engineered eukaryotic protein glycosylation pathway in Escherichia coli. Nat. Chem. Biol., 2012, 8(5), 434-436.
[http://dx.doi.org/10.1038/nchembio.921] [PMID: 22446837]
[99]
Mueller, P.; Gauttam, R.; Raab, N.; Handrick, R.; Wahl, C.; Leptihn, S.; Zorn, M.; Kussmaul, M.; Scheffold, M.; Eikmanns, B.; Elling, L.; Gaisser, S. High level in vivo mucin-type glycosylation in Escherichia coli. Microb. Cell Fact., 2018, 17(1), 168.
[http://dx.doi.org/10.1186/s12934-018-1013-9] [PMID: 30367634]
[100]
Agarwal, S.; Jha, S.; Sanyal, I.; Amla, D.V. Expression and purification of recombinant human alpha1-proteinase inhibitor and its single amino acid substituted variants in Escherichia coli for enhanced stability and biological activity. J. Biotechnol., 2010, 147(1), 64-72.
[http://dx.doi.org/10.1016/j.jbiotec.2010.03.008] [PMID: 20346993]
[101]
Johansen, H.; Sutiphong, J.; Sathe, G.; Jacobs, P.; Cravador, A.; Bollen, A.; Rosenberg, M.; Shatzman, A. High-level production of fully active human alpha 1-antitrypsin in Escherichia coli. Mol. Biol. Med., 1987, 4(5), 291-305.
[PMID: 2826966]
[102]
Straus, S.D.; Fells, G.A.; Wewers, M.D.; Courtney, M.; Tessier, L.H.; Tolstoshev, P.; Lecocq, J.P.; Crystal, R.G. Evaluation of recombinant DNA-directed E.coli produced alpha 1-antitrypsin as an anti-neutrophil elastase for potential use as replacement therapy of alpha 1-antitrypsin deficiency. Biochem. Biophys. Res. Commun., 1985, 130(3), 1177-1184.
[http://dx.doi.org/10.1016/0006-291X(85)91739-5] [PMID: 3896239]
[103]
Courtney, M.; Buchwalder, A.; Tessier, L.H.; Jaye, M.; Benavente, A.; Balland, A.; Kohli, V.; Lathe, R.; Tolstoshev, P.; Lecocq, J.P. High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli. Proc. Natl. Acad. Sci. USA, 1984, 81(3), 669-673.
[http://dx.doi.org/10.1073/pnas.81.3.669] [PMID: 6322161]
[104]
Krishnan, B.; Hedstrom, L.; Hebert, D.N.; Gierasch, L.M.; Gershenson, A. Expression and purification of active recombinant human alpha-1 antitrypsin (AAT) from Escherichia coli. Methods Mol. Biol., 2017, 1639, 195-209.
[http://dx.doi.org/10.1007/978-1-4939-7163-3_19] [PMID: 28752459]
[105]
Vieira Gomes, A.M.; Souza Carmo, T.; Silva Carvalho, L.; Mendonça Bahia, F.; Parachin, N.S. Comparison of yeasts as hosts for recombinant protein production. Microorganisms, 2018, 6(2)E38
[http://dx.doi.org/10.3390/microorganisms6020038] [PMID: 29710826]
[106]
Moir, D.T.; Dumais, D.R. Glycosylation and secretion of human alpha-1-antitrypsin by yeast. Gene, 1987, 56(2-3), 209-217.
[http://dx.doi.org/10.1016/0378-1119(87)90138-7] [PMID: 3315863]
[107]
Kang, H.A.; Nam, S.W.; Kwon, K.S.; Chung, B.H.; Yu, M.H. High-level secretion of human alpha 1-antitrypsin from Saccharomyces cerevisiae using inulinase signal sequence. J. Biotechnol., 1996, 48(1-2), 15-24.
[http://dx.doi.org/10.1016/0168-1656(96)01391-0] [PMID: 8818270]
[108]
Tamer, I.M.; Chisti, Y. Production and recovery of recombinant protease inhibitor α1-antitrypsin. Enzyme Microb. Technol., 2001, 29(10), 611-620.
[http://dx.doi.org/10.1016/S0141-0229(01)00444-6]
[109]
Casolaro, M.A.; Fells, G.; Wewers, M.; Pierce, J.E.; Ogushi, F.; Hubbard, R.; Sellers, S.; Forstrom, J.; Lyons, D.; Kawasaki, G. Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin. J Appl Physiol (1985), 1987, 63(5), 2015-2023.,
[http://dx.doi.org/10.1152/jappl.1987.63.5.2015] [PMID: 3500941]
[110]
Kwon, K.S.; Song, M.; Yu, M.H. Purification and characterization of alpha 1-antitrypsin secreted by recombinant yeast Saccharomyces diastaticus. J. Biotechnol., 1995, 42(3), 191-195.
[http://dx.doi.org/10.1016/0168-1656(95)00079-6] [PMID: 7576538]
[111]
Cereghino, J.L.; Cregg, J.M. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol. Rev., 2000, 24(1), 45-66.
[http://dx.doi.org/10.1111/j.1574-6976.2000.tb00532.x] [PMID: 10640598]
[112]
Bretthauer, R.K. Genetic engineering of Pichia pastoris to humanize N-glycosylation of proteins. Trends Biotechnol., 2003, 21(11), 459-462.
[http://dx.doi.org/10.1016/j.tibtech.2003.09.005] [PMID: 14573354]
[113]
Hasannia, S.; Lotfi, A.S.; Mahboudi, F.; Rezaii, A.; Rahbarizadeh, F.; Mohsenifar, A. Elevated expression of human alpha-1 antitrypsin mediated by yeast intron in Pichia pastoris. Biotechnol. Lett., 2006, 28(19), 1545-1550.
[http://dx.doi.org/10.1007/s10529-006-9121-8] [PMID: 16900336]
[114]
Arjmand, S.; Bidram, E.; Lotfi, A.S.; Shamsara, M.; Mowla, S.J. Expression and purification of functionally active recombinant human alpha 1-antitrypsin in methylotrophic yeast Pichia pastoris. Avicenna J. Med. Biotechnol., 2011, 3(3), 127-134.
[PMID: 23408781]
[115]
Tavasoli, T.; Arjmand, S.; Ranaei Siadat, S.O.; Shojaosadati, S.A.; Sahebghadam Lotfi, A. Enhancement of alpha 1-antitrypsin production in Pichia pastoris by designing and optimizing medium using elemental analysis. Iranian J. Biotechnol., 2017, 15(4), 224-231.
[http://dx.doi.org/10.15171/ijb.1808] [PMID: 29845074]
[116]
Khatami, M.; Hosseini, S.N.; Hasannia, S. Co-expression of alpha-1 antitrypsin with cytoplasmic domain of v-SNARE in Pichia pastoris: Preserving biological activity of alpha-1 antitrypsin. Biotechnol. Appl. Biochem., 2018, 65(2), 181-187.
[http://dx.doi.org/10.1002/bab.1578] [PMID: 28762562]
[117]
Silberstein, D.Z.; Karuppanan, K.; Aung, H.H.; Chen, C.H.; Cross, C.E.; McDonald, K.A. An oxidation-resistant, recombinant alpha-1 antitrypsin produced in Nicotiana benthamiana. Free Radic. Biol. Med., 2018, 120, 303-310.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.03.015] [PMID: 29551638]
[118]
Huang, J.; Sutliff, T.D.; Wu, L.; Nandi, S.; Benge, K.; Terashima, M.; Ralston, A.H.; Drohan, W.; Huang, N.; Rodriguez, R.L. Expression and purification of functional human alpha-1-antitrypsin from cultured plant cells. Biotechnol. Prog., 2001, 17(1), 126-133.
[http://dx.doi.org/10.1021/bp0001516] [PMID: 11170490]
[119]
Zhang, L.; Shi, J.; Jiang, D.; Stupak, J.; Ou, J.; Qiu, Q.; An, N.; Li, J.; Yang, D. Expression and characterization of recombinant human alpha-antitrypsin in transgenic rice seed. J. Biotechnol., 2012, 164(2), 300-308.
[http://dx.doi.org/10.1016/j.jbiotec.2013.01.008] [PMID: 23376844]
[120]
Jha, S.; Agarwal, S.; Sanyal, I.; Amla, D.V. Single-step purification and characterization of a recombinant serine proteinase inhibitor from transgenic plants. Appl. Biochem. Biotechnol., 2016, 179(2), 220-236.
[http://dx.doi.org/10.1007/s12010-016-1989-8] [PMID: 26852026]
[121]
Castilho, A.; Windwarder, M.; Gattinger, P.; Mach, L.; Strasser, R.; Altmann, F.; Steinkellner, H. Proteolytic and N-glycan processing of human α1-antitrypsin expressed in Nicotiana benthamiana. Plant Physiol., 2014, 166(4), 1839-1851.
[http://dx.doi.org/10.1104/pp.114.250720] [PMID: 25355867]
[122]
Yee, C.M.; Zak, A.J.; Hill, B.D.; Wen, F. The coming age of insect cells for manufacturing and development of protein therapeutics. Ind. Eng. Chem. Res., 2018, 57(31), 10061-10070.
[http://dx.doi.org/10.1021/acs.iecr.8b00985] [PMID: 30886455]
[123]
Curtis, H.; Sandoval, C.; Oblin, C.; Difalco, M.R.; Congote, L.F. Insect cell production of a secreted form of human alpha(1)-proteinase inhibitor as a bifunctional protein which inhibits neutrophil elastase and has growth factor-like activities. J. Biotechnol., 2002, 93(1), 35-44.
[http://dx.doi.org/10.1016/S0168-1656(01)00380-7] [PMID: 11690693]
[124]
Morifuji, Y.; Xu, J.; Karasaki, N.; Iiyama, K.; Morokuma, D.; Hino, M.; Masuda, A.; Yano, T.; Mon, H.; Kusakabe, T.; Lee, J.M. Expression, purification, and characterization of recombinant human α1-antitrypsin produced using silkworm-baculovirus expression system. Mol. Biotechnol., 2018, 60(12), 924-934.
[http://dx.doi.org/10.1007/s12033-018-0127-y] [PMID: 30302632]
[125]
Hang, G.D.; Chen, C.J.; Lin, C.Y.; Chen, H.C.; Chen, H. Improvement of glycosylation in insect cells with mammalian glycosyltransferases. J. Biotechnol., 2003, 102(1), 61-71.
[http://dx.doi.org/10.1016/S0168-1656(02)00364-4] [PMID: 12668315]
[126]
Goh, J.B.; Ng, S.K. Impact of host cell line choice on glycan profile. Crit. Rev. Biotechnol., 2018, 38(6), 851-867.
[http://dx.doi.org/10.1080/07388551.2017.1416577] [PMID: 29262720]
[127]
Paterson, T.; Innes, J.; Moore, S. Approaches to maximizing stable expression of alpha 1-antitrypsin in transformed CHO cells. Appl. Microbiol. Biotechnol., 1994, 40(5), 691-698.
[http://dx.doi.org/10.1007/BF00173331] [PMID: 7764427]
[128]
Chin, C.L.; Chin, H.K.; Chin, C.S.; Lai, E.T.; Ng, S.K. Engineering selection stringency on expression vector for the production of recombinant human alpha1-antitrypsin using Chinese hamster ovary cells. BMC Biotechnol., 2015, 15, 44.
[http://dx.doi.org/10.1186/s12896-015-0145-9] [PMID: 26033090]
[129]
Lee, K.J.; Lee, S.M.; Gil, J.Y.; Kwon, O.; Kim, J.Y.; Park, S.J.; Chung, H.S.; Oh, D.B. N-glycan analysis of human α1-antitrypsin produced in Chinese hamster ovary cells. Glycoconj. J., 2013, 30(5), 537-547.
[http://dx.doi.org/10.1007/s10719-012-9453-7] [PMID: 23065139]
[130]
Butler, M.; Spearman, M. The choice of mammalian cell host and possibilities for glycosylation engineering. Curr. Opin. Biotechnol., 2014, 30, 107-112.
[http://dx.doi.org/10.1016/j.copbio.2014.06.010] [PMID: 25005678]
[131]
Lalonde, M.E.; Koyuturk, I.; Brochu, D.; Jabbour, J.; Gilbert, M.; Durocher, Y. Production of α2,6-sialylated and non-fucosylated recombinant alpha-1-antitrypsin in CHO cells. J. Biotechnol., 2020, 307, 87-97.
[http://dx.doi.org/10.1016/j.jbiotec.2019.10.021] [PMID: 31697975]
[132]
Amann, T.; Hansen, A.H.; Kol, S.; Hansen, H.G.; Arnsdorf, J.; Nallapareddy, S.; Voldborg, B.; Lee, G.M.; Andersen, M.R.; Kildegaard, H.F. Glyco-engineered CHO cell lines producing alpha-1-antitrypsin and C1 esterase inhibitor with fully humanized N-glycosylation profiles. Metab. Eng., 2019, 52, 143-152.
[http://dx.doi.org/10.1016/j.ymben.2018.11.014] [PMID: 30513349]
[133]
Pallister, E.G.; Choo, M.S.F.; Tai, J.N.; Leong, D.S.Z.; Tang, W.Q.; Ng, S.K.; Huang, K.; Marchesi, A.; Both, P.; Gray, C.; Rudd, P.M.; Flitsch, S.L.; Nguyen-Khuong, T. Exploiting the disialyl galactose activity of α2,6-sialyltransferase from Photobacterium damselae To generate a highly sialylated recombinant α-1-antitrypsin. Biochemistry, 2020, 59(34), 3123-3128.
[http://dx.doi.org/10.1021/acs.biochem.9b00563] [PMID: 31580652]
[134]
Janesch, B.; Saxena, H.; Sim, L.; Wakarchuk, W.W. Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins. Glycobiology, 2019, 29(10), 735-747.
[http://dx.doi.org/10.1093/glycob/cwz050] [PMID: 31281932]
[135]
Blanchard, V.; Liu, X.; Eigel, S.; Kaup, M.; Rieck, S.; Janciauskiene, S.; Sandig, V.; Marx, U.; Walden, P.; Tauber, R.; Berger, M. N-glycosylation and biological activity of recombinant human alpha1-antitrypsin expressed in a novel human neuronal cell line. Biotechnol. Bioeng., 2011, 108(9), 2118-2128.
[http://dx.doi.org/10.1002/bit.23158] [PMID: 21495009]
[136]
Ross, D.; Brown, T.; Harper, R.; Pamarthi, M.; Nixon, J.; Bromirski, J.; Li, C.M.; Ghali, R.; Xie, H.; Medvedeff, G.; Li, H.; Scuderi, P.; Arora, V.; Hunt, J.; Barnett, T. Production and characterization of a novel human recombinant alpha-1-antitrypsin in PER.C6 cells. J. Biotechnol., 2012, 162(2-3), 262-273.
[http://dx.doi.org/10.1016/j.jbiotec.2012.09.018] [PMID: 23036927]
[137]
Jaberie, H.; Naghibalhossaini, F. Recombinant production of native human α-1-antitrypsin protein in the liver HepG2 cells. Biotechnol. Lett., 2016, 38(10), 1683-1690.
[http://dx.doi.org/10.1007/s10529-016-2150-z] [PMID: 27314477]
[138]
Scott, B.M.; Sheffield, W.P. Engineering the serpin α1 -antitrypsin: a diversity of goals and techniques. Protein Sci., 2020, 29(4), 856-871.
[http://dx.doi.org/10.1002/pro.3794] [PMID: 31774589]
[139]
Zhu, W.; Li, L.; Deng, M.; Wang, B.; Li, M.; Ding, G.; Yang, Z.; Medynski, D.; Lin, X.; Ouyang, Y.; Lin, J.; Li, L.; Lin, X. Oxidation-resistant and thermostable forms of alpha-1 antitrypsin from Escherichia coli inclusion bodies. FEBS Open Bio, 2018, 8(10), 1711-1721.
[http://dx.doi.org/10.1002/2211-5463.12515] [PMID: 30338221]
[140]
Pirooznia, N.; Hasannia, S.; Arab, S.S.; Lotfi, A.S.; Ghanei, M.; Shali, A. The design of a new truncated and engineered alpha1-antitrypsin based on theoretical studies: an antiprotease therapeutics for pulmonary diseases. Theor. Biol. Med. Model., 2013, 10, 36.
[http://dx.doi.org/10.1186/1742-4682-10-36] [PMID: 23705923]
[141]
Zhang, N.; Wright, T.; Caraway, P.; Xu, J. Enhanced secretion of human α1-antitrypsin expressed with a novel glycosylation module in tobacco BY-2 cell culture. Bioengineered, 2019, 10(1), 87-97.
[http://dx.doi.org/10.1080/21655979.2019.1604037] [PMID: 30957636]
[142]
Czajkowsky, D.M.; Hu, J.; Shao, Z.; Pleass, R.J. Fc-fusion proteins: new developments and future perspectives. EMBO Mol. Med., 2012, 4(10), 1015-1028.
[http://dx.doi.org/10.1002/emmm.201201379] [PMID: 22837174]
[143]
Lee, S.; Lee, Y.; Hong, K.; Hong, J.; Bae, S.; Choi, J.; Jhun, H.; Kwak, A.; Kim, E.; Jo, S.; Dinarello, C.A.; Kim, S. Effect of recombinant α1-antitrypsin Fc-fused (AAT-Fc)protein on the inhibition of inflammatory cytokine production and streptozotocin-induced diabetes. Mol. Med., 2013, 19, 65-71.
[http://dx.doi.org/10.2119/molmed.2012.00308] [PMID: 23552726]
[144]
Joosten, L.A.; Crişan, T.O.; Azam, T.; Cleophas, M.C.; Koenders, M.I.; van de Veerdonk, F.L.; Netea, M.G.; Kim, S.; Dinarello, C.A. Alpha-1-anti-trypsin-Fc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1β and by the induction of endogenous IL-1Ra. Ann. Rheum. Dis., 2016, 75(6), 1219-1227.
[http://dx.doi.org/10.1136/annrheumdis-2014-206966] [PMID: 26174021]
[145]
Toldo, S.; Mauro, A.G.; Marchetti, C.; Rose, S.W.; Mezzaroma, E.; Van Tassell, B.W.; Kim, S.; Dinarello, C.A.; Abbate, A. Recombinant human alpha-1 antitrypsin-Fc fusion protein reduces mouse myocardial inflammatory injury after ischemia-reperfusion independent of elastase inhibition. J. Cardiovasc. Pharmacol., 2016, 68(1), 27-32.
[http://dx.doi.org/10.1097/FJC.0000000000000383] [PMID: 26945157]
[146]
Harris, J.M.; Chess, R.B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov., 2003, 2(3), 214-221.
[http://dx.doi.org/10.1038/nrd1033] [PMID: 12612647]
[147]
Bye, J.W.; Platts, L.; Falconer, R.J. Biopharmaceutical liquid formulation: a review of the science of protein stability and solubility in aqueous environments. Biotechnol. Lett., 2014, 36(5), 869-875.
[http://dx.doi.org/10.1007/s10529-013-1445-6] [PMID: 24557073]
[148]
Kolarich, D.; Turecek, P.L.; Weber, A.; Mitterer, A.; Graninger, M.; Matthiessen, P.; Nicolaes, G.A.; Altmann, F.; Schwarz, H.P. Biochemical, molecular characterization, and glycoproteomic analyses of alpha(1)-proteinase inhibitor products used for replacement therapy. Transfusion, 2006, 46(11), 1959-1977.
[http://dx.doi.org/10.1111/j.1537-2995.2006.01004.x] [PMID: 17076852]
[149]
Sieluk, J.; Levy, J.; Sandhaus, R.A.; Silverman, H.; Holm, K.E.; Mullins, C.D. Costs of Medical care among augmentation therapy users and non-users with alpha-1 antitrypsin deficiency in the United States. Chronic Obstr. Pulm. Dis. (Miami), 2018, 6(1), 6-16.
[http://dx.doi.org/10.15326/jcopdf.6.1.2017.0187] [PMID: 30775420]
[150]
Sieluk, J.; Slejko, J.F.; Silverman, H.; Perfetto, E.; Mullins, C.D. Medical costs of Alpha-1 antitrypsin deficiency-associated COPD in the United States. Orphanet J. Rare Dis., 2020, 15(1), 260.
[http://dx.doi.org/10.1186/s13023-020-01523-4] [PMID: 32967697]
[151]
Arora, V.; Cruz, M.; Lang, J.; Klos, A.M.; Merritt, W.K.; Price, J.; Taylor, G.; Vandeberg, P.; Wee, K.; Willis, T. Comparison of the liquid and lyophilized formulations of Prolastin(R)-C for Alpha1-Antitrypsin deficiency: Biochemical characteristics, pharmacokinetics, safety and neoantigenicity in rabbits. Biologicals, 2019, 62, 77-84.
[http://dx.doi.org/10.1016/j.biologicals.2019.09.002] [PMID: 31522909]
[152]
Stocks, J.M.; Brantly, M.L.; Wang-Smith, L.; Campos, M.A.; Chapman, K.R.; Kueppers, F.; Sandhaus, R.A.; Strange, C.; Turino, G. Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha1-antitrypsin deficiency: a randomized study. BMC Clin. Pharmacol., 2010, 10, 13.
[http://dx.doi.org/10.1186/1472-6904-10-13] [PMID: 20920295]
[153]
Brantly, M.L.; Lascano, J.E.; Shahmohammadi, A. Intravenous alpha-1 antitrypsin therapy for alpha-1 antitrypsin deficiency: the current state of the evidence. Chronic Obstr. Pulm. Dis. (Miami), 2018, 6(1), 100-114.
[http://dx.doi.org/10.15326/jcopdf.6.1.2017.0185] [PMID: 30775428]
[154]
Turner, A.M. Alpha-1 antitrypsin deficiency: new developments in augmentation and other therapies. BioDrugs, 2013, 27(6), 547-558.
[http://dx.doi.org/10.1007/s40259-013-0042-5] [PMID: 23771682]
[155]
Siekmeier, R. Lung deposition of inhaled alpha-1-proteinase inhibitor (alpha 1-PI) - problems and experience of alpha1-PI inhalation therapy in patients with hereditary alpha1-PI deficiency and cystic fibrosis. Eur. J. Med. Res., 2010, 15(Suppl. 2), 164-174.
[http://dx.doi.org/10.1186/2047-783X-15-S2-164] [PMID: 21147646]
[156]
Mohanka, M.; Khemasuwan, D.; Stoller, J.K. A review of augmentation therapy for alpha-1 antitrypsin deficiency. Expert Opin. Biol. Ther., 2012, 12(6), 685-700.
[http://dx.doi.org/10.1517/14712598.2012.676638] [PMID: 22500781]
[157]
Stolk, J.; Tov, N.; Chapman, K.R.; Fernandez, P.; MacNee, W.; Hopkinson, N.S.; Piitulainen, E.; Seersholm, N.; Vogelmeier, C.F.; Bals, R.; McElvaney, G.; Stockley, R.A. Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD. Eur. Respir. J., 2019, 54(5)1900673
[http://dx.doi.org/10.1183/13993003.00673-2019] [PMID: 31467115]
[158]
Newman, S.P. Drug delivery to the lungs: challenges and opportunities. Ther. Deliv., 2017, 8(8), 647-661.
[http://dx.doi.org/10.4155/tde-2017-0037] [PMID: 28730933]
[159]
Lockett, A.D.; Brown, M.B.; Santos-Falcon, N.; Rush, N.I.; Oueini, H.; Oberle, A.J.; Bolanis, E.; Fragoso, M.A.; Petrusca, D.N.; Serban, K.A.; Schweitzer, K.S.; Presson, R.G., Jr; Campos, M.; Petrache, I. Active trafficking of alpha 1 antitrypsin across the lung endothelium. PLoS One, 2014, 9(4)e93979
[http://dx.doi.org/10.1371/journal.pone.0093979] [PMID: 24743137]
[160]
Griese, M.; Scheuch, G. Delivery of alpha-1 antitrypsin to airways. Ann. Am. Thorac. Soc., 2016, 13(Suppl. 4), S346-S351.
[http://dx.doi.org/10.1513/AnnalsATS.201507-469KV] [PMID: 27564672]
[161]
Usmani, O.S. Feasibility of aerosolized alpha-1 antitrypsin as a therapeutic option. Chronic Obstr. Pulm. Dis. (Miami), 2020, 7(3), 272-279.
[http://dx.doi.org/10.15326/jcopdf.7.3.2019.0179] [PMID: 32726075]
[162]
Bodier-Montagutelli, E.; Mayor, A.; Vecellio, L.; Respaud, R.; Heuzé-Vourc’h, N. Designing inhaled protein therapeutics for topical lung delivery: what are the next steps? Expert Opin. Drug Deliv., 2018, 15(8), 729-736.
[http://dx.doi.org/10.1080/17425247.2018.1503251] [PMID: 30025210]
[163]
Geller, D.E. The science of aerosol delivery in cystic fibrosis. Pediatr. Pulmonol., 2008, 43(S9), S5-S17.
[http://dx.doi.org/10.1002/ppul.20860]
[164]
Hubbard, R.C.; Casolaro, M.A.; Mitchell, M.; Sellers, S.E.; Arabia, F.; Matthay, M.A.; Crystal, R.G. Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance. Proc. Natl. Acad. Sci. USA, 1989, 86(2), 680-684.
[http://dx.doi.org/10.1073/pnas.86.2.680] [PMID: 2783491]
[165]
Griese, M.; Latzin, P.; Kappler, M.; Weckerle, K.; Heinzlmaier, T.; Bernhardt, T.; Hartl, D. alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients. Eur. Respir. J., 2007, 29(2), 240-250.
[http://dx.doi.org/10.1183/09031936.00047306] [PMID: 17050563]
[166]
Loira-Pastoriza, C.; Todoroff, J.; Vanbever, R. Delivery strategies for sustained drug release in the lungs. Adv. Drug Deliv. Rev., 2014, 75, 81-91.
[http://dx.doi.org/10.1016/j.addr.2014.05.017] [PMID: 24915637]
[167]
Brand, P.; Beckmann, H.; Maas Enriquez, M.; Meyer, T.; Müllinger, B.; Sommerer, K.; Weber, N.; Weuthen, T.; Scheuch, G. Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices. Eur. Respir. J., 2003, 22(2), 263-267.
[http://dx.doi.org/10.1183/09031936.03.00096802] [PMID: 12952258]
[168]
Brand, P.; Schulte, M.; Wencker, M.; Herpich, C.H.; Klein, G.; Hanna, K.; Meyer, T. Lung deposition of inhaled alpha1-proteinase inhibitor in cystic fibrosis and alpha1-antitrypsin deficiency. Eur. Respir. J., 2009, 34(2), 354-360.
[http://dx.doi.org/10.1183/09031936.00118408] [PMID: 19251783]
[169]
Geller, D.E.; Kesser, K.C. The I-neb adaptive aerosol delivery system enhances delivery of alpha1-antitrypsin with controlled inhalation. J. Aerosol Med. Pulm. Drug Deliv., 2010, 23(Suppl. 1), S55-S59.
[http://dx.doi.org/10.1089/jamp.2009.0793] [PMID: 20373910]
[170]
Martin, S.L.; Downey, D.; Bilton, D.; Keogan, M.T.; Edgar, J.; Elborn, J.S.; Recombinant, A.A.T.C.F.S.T. Recombinant AAT CF Study Team. Safety and efficacy of recombinant alpha(1)-antitrypsin therapy in cystic fibrosis. Pediatr. Pulmonol., 2006, 41(2), 177-183.
[http://dx.doi.org/10.1002/ppul.20345] [PMID: 16372352]
[171]
Monk, R.; Graves, M.; Williams, P.; Strange, C. Inhaled alpha 1-antitrypsin: gauging patient interest in a new treatment. COPD, 2013, 10(4), 411-415.
[http://dx.doi.org/10.3109/15412555.2012.758698] [PMID: 23537112]
[172]
Pilcer, G.; Amighi, K. Formulation strategy and use of excipients in pulmonary drug delivery. Int. J. Pharm., 2010, 392(1-2), 1-19.
[http://dx.doi.org/10.1016/j.ijpharm.2010.03.017] [PMID: 20223286]
[173]
de Boer, A.H.; Hagedoorn, P.; Hoppentocht, M.; Buttini, F.; Grasmeijer, F.; Frijlink, H.W. Dry powder inhalation: past, present and future. Expert Opin. Drug Deliv., 2017, 14(4), 499-512.
[http://dx.doi.org/10.1080/17425247.2016.1224846] [PMID: 27534768]
[174]
Quarta, E.; Chierici, V.; Flammini, L.; Tognolini, M.; Barocelli, E.; Cantoni, A.M.; Dujovny, G.; Ecenarro Probst, S.; Sonvico, F.; Colombo, G.; Rossi, A.; Bettini, R.; Colombo, P.; Buttini, F. Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats. J. Control. Release, 2020, 323, 412-420.
[http://dx.doi.org/10.1016/j.jconrel.2020.04.015] [PMID: 32325175]
[175]
Geller, D.E.; Weers, J.; Heuerding, S. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J. Aerosol Med. Pulm. Drug Deliv., 2011, 24(4), 175-182.
[http://dx.doi.org/10.1089/jamp.2010.0855] [PMID: 21395432]
[176]
Pontes, J.F.; Grenha, A. Multifunctional nanocarriers for lung drug delivery. Nanomaterials (Basel), 2020, 10(2)E183
[http://dx.doi.org/10.3390/nano10020183] [PMID: 31973051]
[177]
Pirooznia, N.; Hasannia, S.; Lotfi, A.S.; Ghanei, M. Encapsulation of alpha-1 antitrypsin in PLGA nanoparticles: in vitro characterization as an effective aerosol formulation in pulmonary diseases. J. Nanobiotechnology, 2012, 10, 20.
[http://dx.doi.org/10.1186/1477-3155-10-20] [PMID: 22607686]
[178]
Fredenberg, S.; Wahlgren, M.; Reslow, M.; Axelsson, A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-a review. Int. J. Pharm., 2011, 415(1-2), 34-52.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.049] [PMID: 21640806]
[179]
Ghasemi, A.; Mohtashami, M.; Sheijani, S.S.; Aliakbari, K. Chitosan-genipin nanohydrogel as a vehicle for sustained delivery of alpha-1 antitrypsin. Res. Pharm. Sci., 2015, 10(6), 523-534.
[PMID: 26779272]
[180]
Heyder, J.; Gebhart, J.; Rudolf, G.; Schiller, C.F.; Stahlhofen, W. Deposition of particles in the human respiratory tract in the size range 0.005-15 μm. J. Aerosol Sci., 1986, 17(5), 811-825.
[http://dx.doi.org/10.1016/0021-8502(86)90035-2]
[181]
Mejias, J.C.; Roy, K. In-vitro and in-vivo characterization of a multi-stage enzyme-responsive nanoparticle-in-microgel pulmonary drug delivery system. J. Control. Disease., 2019, 316, 393-403.
[http://dx.doi.org/10.1016/j.jconrel.2019.09.012] [PMID: 31715279]
[182]
Mueller, C.; Flotte, T.R. Gene-based therapy for alpha-1 antitrypsin deficiency. COPD, 2013, 10(Suppl. 1), 44-49.
[http://dx.doi.org/10.3109/15412555.2013.764978] [PMID: 23527792]
[183]
Lorincz, R.; Curiel, D.T. Advances in alpha-1 antitrypsin gene therapy. Am. J. Respir. Cell Mol. Biol., 2020, 63(5), 560-570.
[http://dx.doi.org/10.1165/rcmb.2020-0159PS] [PMID: 32668173]
[184]
Gruntman, A.M.; Flotte, T.R. Therapeutics: gene therapy for alpha-1 antitrypsin deficiency. Methods Mol. Biol., 2017, 1639, 267-275.
[http://dx.doi.org/10.1007/978-1-4939-7163-3_27] [PMID: 28752467]
[185]
Song, S.; Morgan, M.; Ellis, T.; Poirier, A.; Chesnut, K.; Wang, J.; Brantly, M.; Muzyczka, N.; Byrne, B.J.; Atkinson, M.; Flotte, T.R. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. USA, 1998, 95(24), 14384-14388.
[http://dx.doi.org/10.1073/pnas.95.24.14384] [PMID: 9826709]
[186]
Sosulski, M.L.; Stiles, K.M.; Frenk, E.Z.; Hart, F.M.; Matsumura, Y.; De, B.P.; Kaminsky, S.M.; Crystal, R.G. Gene therapy for alpha 1-antitrypsin deficiency with an oxidant-resistant human alpha 1-antitrypsin. JCI Insight, 2020, 5(15)135951
[http://dx.doi.org/10.1172/jci.insight.135951] [PMID: 32759494]
[187]
Ma, H.; Lu, Y.; Lowe, K.; van der Meijden-Erkelens, L.; Wasserfall, C.; Atkinson, M.A.; Song, S. Regulated hAAT expression from a novel rAAV vector and its application in the prevention of type 1 diabetes. J. Clin. Med., 2019, 8(9)E1321
[http://dx.doi.org/10.3390/jcm8091321] [PMID: 31466263]
[188]
Song, C.Q.; Wang, D.; Jiang, T.; O’Connor, K.; Tang, Q.; Cai, L.; Li, X.; Weng, Z.; Yin, H.; Gao, G.; Mueller, C.; Flotte, T.R.; Xue, W. In vivo genome editing partially restores alpha1-antitrypsin in a murine model of Aat deficiency. Hum. Gene Ther., 2018, 29(8), 853-860.
[http://dx.doi.org/10.1089/hum.2017.225] [PMID: 29597895]
[189]
Wooddell, C.I.; Blomenkamp, K.; Peterson, R.M.; Subbotin, V.M.; Schwabe, C.; Hamilton, J.; Chu, Q.; Christianson, D.R.; Hegge, J.O.; Kolbe, J.; Hamilton, H.L.; Branca-Afrazi, M.F.; Given, B.D.; Lewis, D.L.; Gane, E.; Kanner, S.B.; Teckman, J.H. Development of an RNAi therapeutic for alpha-1-antitrypsin liver disease. JCI Insight, 2020, 5(12)135348
[http://dx.doi.org/10.1172/jci.insight.135348] [PMID: 32379724]
[190]
Berthelier, V.; Harris, J.B.; Estenson, K.N.; Baudry, J. Discovery of an inhibitor of Z-alpha1 antitrypsin polymerization. PLoS One, 2015, 10(5)e0126256
[http://dx.doi.org/10.1371/journal.pone.0126256] [PMID: 25961288]
[191]
Lomas, D.A.; Irving, J.A.; Arico-Muendel, C.; Belyanskaya, S.; Brewster, A.; Brown, M.; Chung, C-w.; Dave, H.; Denis, A.; Dodic, N.; Dossang, A.; Eddershaw, P.; Klimaszewska, D.; Haq, I.; Holmes, D.S.; Hutchinson, J.P.; Jagger, A.; Jakhria, T.; Jigorel, E.; Liddle, J.; Lind, K.; Marciniak, S.J.; Messer, J.; Neu, M.; Olszewski, A.; Ordonez, A.; Ronzoni, R.; Rowedder, J.; Rüdiger, M.; Skinner, S.; Smith, K.J.; Terry, R.; Trottet, L.; Uings, I.; Wilson, S.; Zhu, Z.; Pearce, A.C. Development of a small molecule that corrects misfolding and increases secretion of Z α1-antitrypsin. bioRxiv, 2020. preprint..
[http://dx.doi.org/10.1101/2020.07.26.217661]
[192]
Zhang, X.; Pham, K.; Li, D.; Schutte, R.J.; Gonzalo, D.H.; Zhang, P.; Oshins, R.; Tan, W.; Brantly, M.; Liu, C.; Ostrov, D.A. A novel small molecule inhibits intrahepatocellular accumulation of z-variant alpha 1-antitrypsin in vitro and in vivo. Cells, 2019, 8(12)E1586
[http://dx.doi.org/10.3390/cells8121586] [PMID: 31817705]
[193]
Sullivan, G.P.; Davidovich, P.B.; Sura-Trueba, S.; Belotcerkovskaya, E.; Henry, C.M.; Clancy, D.M.; Zinoveva, A.; Mametnabiev, T.; Garabadzhiu, A.V.; Martin, S.J. Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation. FEBS Open Bio, 2018, 8(5), 751-763.
[http://dx.doi.org/10.1002/2211-5463.12406] [PMID: 29744290]
[194]
Schepetkin, I.A.; Khlebnikov, A.I.; Quinn, M.T. N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. J. Med. Chem., 2007, 50(20), 4928-4938.
[http://dx.doi.org/10.1021/jm070600+] [PMID: 17850059]

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