Gene therapy for alpha-1 antitrypsin deficiency: an update

References

• Rahaghi FF. Alpha-1 antitrypsin deficiency research and emerging treatment strategies: what’s down the road? Ther Adv Chronic Dis. 2021;12:20406223211014024.
   Web of Science ®Google Scholar
• Strnad P, McElvaney NG, Lomas DA. Alpha1-Antitrypsin Deficiency. N Engl J Med. 2020;382:1443–1455. .
   PubMed Web of Science ®Google Scholar
• Sapey E. Neutrophil modulation in alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2020;7:247–259.
   PubMed Web of Science ®Google Scholar
• Flotte TR. Alpha-1 Antitrypsin Deficiency as a Candidate for Gene Editing. Hum Gene Ther. 2018;29:843–844.
   PubMed Web of Science ®Google Scholar
• Fromme M, Schneider CV, Trautwein C, et al. Alpha-1 antitrypsin deficiency: a re-surfacing adult liver disorder. J Hepatol. 2022;76:946–958.
   PubMed Web of Science ®Google Scholar
• Strange C. Alpha-1 Antitrypsin Deficiency Associated COPD. Chronic Obstr Pulm Dis. 2020;41:339–345.
   Google Scholar
• Cazzola M, Stolz D, Rogliani P, et al. α1-Antitrypsin deficiency and chronic respiratory disorders. Eur Respir Rev. 2020;29:190073.
   PubMed Web of Science ®Google Scholar
• Sandhaus RA, Strange C, Zanichelli A, et al. Improving the Lives of Patients with Alpha-1 Antitrypsin Deficiency. Int J Chron Obstruct Pulmon Dis. 2020;15:3313–3322.
   PubMed Web of Science ®Google Scholar
• Ferrarotti I, Ottaviani S, De Silvestri A, et al. Update on α1-antitrypsin deficiency. Breathe. 2018;14:e17.
   Web of Science ®Google Scholar
• Townsend SA, Edgar RG, Ellis PR, et al. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther. 2018;47:877–885.
   PubMed Web of Science ®Google Scholar
• Courtney M, Buchwalder A, Tessier LH, et al. High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli. Proc Natl Acad Sci. 1984;81:669–673.
   PubMed Web of Science ®Google Scholar
• Tamer IM, Chisti Y. Production and recovery of recombinant protease inhibitor α1-antitrypsin. Enzyme Microb Technol. 2001;29:611–620.
   Web of Science ®Google Scholar
• Ghaedi M, Sahebghadam Lotfi A, Soleimani M, et al. Expression of Recombinant Alpha-1 Antitrypsin in CHO and COS-7 Cell Lines Using Lentiviral Vector. Iran J Biotechnol. 2009;7:148–156.
   Google Scholar
• Falkenhagen A, Asad S, Read SE, et al. Lentiviral expression system for the purification of secreted proteins from human cell cultures. BMC Biotechnol. 2016;16:66.
   PubMed Web of Science ®Google Scholar
• Bjursell M, Porritt MJ, Ericson E, et al. Therapeutic Genome Editing With CRISPR/Cas9 in a Humanized Mouse Model Ameliorates α1-antitrypsin Deficiency Phenotype. EBioMedicine. 2018;29:104–111.
   PubMed Web of Science ®Google Scholar
• Shen S, Sanchez ME, Blomenkamp K, et al. Amelioration of Alpha-1 Antitrypsin Deficiency Diseases with Genome Editing in Transgenic Mice. Hum Gene Ther. 2018;29:861–873.
   PubMed Web of Science ®Google Scholar
• Quinn M, Ellis P, Pye A, et al. Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: current Perspectives. Ther Clin Risk Manag. 2020;16:1243–1255.
   PubMed Web of Science ®Google Scholar
• Pye A, Turner AM. Experimental and investigational drugs for the treatment of alpha-1 antitrypsin deficiency. Expert Opin Investig Drugs. 2019;28:891–902.
   PubMed Web of Science ®Google Scholar
• Flotte TR, Mueller C. Gene therapy for alpha-1 antitrypsin deficiency. Hum Mol Genet. 2011;20:R87–R92.
   PubMed Web of Science ®Google Scholar
• Gruntman AM, Flotte TR. Therapeutics: gene Therapy for Alpha-1 Antitrypsin Deficiency. Borel F, Mueller C. editors Alpha-1 Antitrypsin Defic Methods Protoc [Internet]. New York NY Springer New York 2017. 267–275. Available from
   Google Scholar
• Chiuchiolo MJ, Crystal RG. Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease. Ann Am Thorac Soc. 2016;13:S352–S369.
   PubMed Web of Science ®Google Scholar
• Ledley FD, Woo SLC. Molecular basis of α1-antitrypsin deficiency and its potential therapy by gene transfer. J Inherit Metab Dis. 1986;9:85–91.
   PubMed Web of Science ®Google Scholar
• Ledley FD, Grenett HE, McGinnis-Shelnutt M, et al. Retroviral-mediated gene transfer of human phenylalanine hydroxylase into NIH 3T3 and hepatoma cells. Proc Natl Acad Sci. 1986;83:409–413.
   PubMed Web of Science ®Google Scholar
• Garver RI, Chytil A, Karlsson S, et al. Production of Glycosylated Physiologically “Normal” Human α 1-antitrypsin by Mouse Fibroblasts Modified by Insertion of a Human α 1-antitrypsin cDNA Using a Retroviral Vector. Proc Natl Acad Sci U S A. 1987;84:1050–1054.
   PubMed Web of Science ®Google Scholar
• Garver RI, Chytil A, Courtney M, et al. Clonal Gene Therapy: transplanted Mouse Fibroblast Clones Express Human α1-Antitrypsin Gene in Vivo. Science. 1987;237:762–764.
   PubMed Web of Science ®Google Scholar
• Rosenfeld MA, Siegfried W, Yoshimura K, et al. Adenovirus-Mediated Transfer of a Recombinant α1-Antitrypsin Gene to the Lung Epithelium in Vivo. Science. 1991;252:431–434.
   PubMed Web of Science ®Google Scholar
• Wozniak J, Wandtke T, Kopinski P, et al. Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy. Hum Gene Ther. 2015;26:709–718.
   PubMed Web of Science ®Google Scholar
• Kay MA, Baley P, Rothenberg S, et al. Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc Natl Acad Sci. 1992;89:89–93.
   PubMed Web of Science ®Google Scholar
• Kay MA, Graham F, Leland F, et al. Therapeutic serum concentrations of human alpha-1 antitrypsin after adenoviral-mediated gene transfer into mouse hepatocytes. Hepatology. 1995;21:815–819.
   PubMed Web of Science ®Google Scholar
• Gregory SM, Nazir SA, Metcalf JP. Implications of the innate immune response to adenovirus and adenoviral vectors. Future Virol. 2011;6:357–374.
   PubMed Web of Science ®Google Scholar
• Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, et al. Current Clinical Applications of In Vivo Gene Therapy with AAVs. Mol Ther. 2021;29:464–488.
   PubMed Web of Science ®Google Scholar
• Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18:358–378.
   PubMed Web of Science ®Google Scholar
• Gruntman AM, Flotte TR. Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency. Hum Gene Ther Methods. 2015;26:77–81.
   PubMed Web of Science ®Google Scholar
• Lorincz R, Curiel DT. Advances in Alpha-1 Antitrypsin Gene Therapy. Am J Respir Cell Mol Biol. 2020;63:560–570.
   PubMed Web of Science ®Google Scholar
• Song S, Morgan M, Ellis T, et al. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc Natl Acad Sci. 1998;95:14384–14388.
   PubMed Web of Science ®Google Scholar
• Poirier AE, Combee LA, Martino A, et al. Toxicology and Biodistribution Studies of a Recombinant Adeno-Associated Virus 2 (rAAV2) Alpha-1 Antitrypsin (AAT) Vector. Mol Ther. 2004;9:S40.
   Web of Science ®Google Scholar
• Brigham KL, Lane KB, Meyrick B, et al. Transfection of Nasal Mucosa with a Normal alpha1-Antitrypsin Gene in alpha1-Antitrypsin-Deficient Subjects: comparison with Protein Therapy. Hum Gene Ther. 2000;11:1023–1032.
   PubMed Web of Science ®Google Scholar
• Flotte TR, Brantly ML, Spencer LT, et al. Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV2-CB-hAAT) Gene Vector to AAT-Deficient Adults. Hum Gene Ther. 2004;15:93–128.
   PubMed Web of Science ®Google Scholar
• Brantly ML, Spencer LT, Humphries M, et al. Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Serotype 2 α1-Antitrypsin (AAT) Vector in AAT-Deficient Adults. Hum Gene Ther. 2006;17:1177–1186.
   PubMed Web of Science ®Google Scholar
• Brantly ML, Chulay JD, Wang L, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci. 2009;106:16363–16368.
   PubMed Web of Science ®Google Scholar
• Flotte TR, Trapnell BC, Humphries M, et al. Phase 2 Clinical Trial of a Recombinant Adeno-Associated Viral Vector Expressing α1-Antitrypsin: interim Results. Hum Gene Ther. 2011;22:1239–1247.
   PubMed Web of Science ®Google Scholar
• Mueller C, Chulay JD, Trapnell BC, et al. Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. J Clin Invest. 2013;123:5310–5318.
   PubMed Web of Science ®Google Scholar
• Ertl HCJ. T Cell-Mediated Immune Responses to AAV and AAV Vectors. Front Immunol [Internet]. 2021;12. [cited 2023 Jan 23]. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2021.666666.
   Google Scholar
• Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1–mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. Blood. 2009;114:2077–2086.
   PubMed Web of Science ®Google Scholar
• Mueller C, Gernoux G, Gruntman AM, et al. 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency. Mol Ther J Am Soc Gene Ther. 2017 [april 10];25:1387–1394.
   PubMed Web of Science ®Google Scholar
• Arjomandnejad M, Sylvia K, Blackwood M, et al. Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells. Mol Ther - Methods Clin Dev. 2021;23:490–506.
   PubMed Web of Science ®Google Scholar
• Gruntman AM, Gernoux G, Tang Q, et al. Bridging from Intramuscular to Limb Perfusion Delivery of rAAV: optimization in a Non-human Primate Study. Mol Ther - Methods Clin Dev. 2019;13:233–242.
   PubMed Web of Science ®Google Scholar
• Gernoux G, Gruntman AM, Blackwood M, et al. Muscle-Directed Delivery of an AAV1 Vector Leads to Capsid-Specific T Cell Exhaustion in Nonhuman Primates and Humans. Mol Ther. 2020;28:747–757.
   PubMed Web of Science ®Google Scholar
• Greig JA, Peng H, Ohlstein J, et al. Intramuscular Injection of AAV8 in Mice and Macaques Is Associated with Substantial Hepatic Targeting and Transgene Expression. PLOS ONE. 2014;9:e112268.
   PubMed Web of Science ®Google Scholar
• De B, Heguy A, Leopold PL, et al. Intrapleural administration of a serotype 5 adeno-associated virus coding for α1-antitrypsin mediates persistent, high lung and serum levels of α1-antitrypsin. Mol Ther. 2004;10:1003–1010.
   PubMed Web of Science ®Google Scholar
• Duncan GA, Kim N, Colon-Cortes Y, et al. An Adeno-Associated Viral Vector Capable of Penetrating the Mucus Barrier to Inhaled Gene Therapy. Mol Ther - Methods Clin Dev. 2018;9:296–304.
   PubMed Web of Science ®Google Scholar
• Wang RL, McLaughlin T, Cossette T, et al. Recombinant AAV Serotype and Capsid Mutant Comparison for Pulmonary Gene Transfer of α-1-Antitrypsin Using Invasive and Noninvasive Delivery. Mol Ther. 2009;17:81–87.
   PubMed Web of Science ®Google Scholar
• Martini SV, Fagundes SS, Schmidt AC, et al. Does the use of recombinant AAV5 in pulmonary gene therapy lead to lung damage? Respir Physiol Neurobiol. 2009;168:203–209.
   PubMed Web of Science ®Google Scholar
• Lee GK, Maheshri N, Kaspar B, et al. PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol Bioeng. 2005;92:24–34.
   PubMed Web of Science ®Google Scholar
• da Silva AL, Martini SV, Abreu SC, et al. DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma. J Control Release. 2014;180:125–133.
   PubMed Web of Science ®Google Scholar
• da Silva AL, de Oliveira GP, Kim N, et al. Nanoparticle-based thymulin gene therapy therapeutically reverses key pathology of experimental allergic asthma. Sci Adv. 2020;6:eaay7973.
   PubMed Web of Science ®Google Scholar
• Heguy A, Crystal RG. Intrapleural “outside-in” gene therapy: therapeutics for organs of the chest via gene transfer to the pleura. Curr Opin Mol Ther. 2005;7:440–453.
   PubMedGoogle Scholar
• McClain LE, Davey MG, Zoltick PW, et al. Vector serotype screening for use in ovine perinatal lung gene therapy. J Pediatr Surg. 2016;51:879–884.
   PubMed Web of Science ®Google Scholar
• Martini SV, da Silva AL, Ferreira D, et al. Single Tyrosine Mutation in AAV8 Vector Capsid Enhances Gene Lung Delivery and Does Not Alter Lung Morphofunction in Mice. Cell Physiol Biochem. 2014;34:681–690.
   PubMedGoogle Scholar
• Martini SV, Silva AL, Ferreira D, et al. Tyrosine Mutation in AAV9 Capsid Improves Gene Transfer to the Mouse Lung. Cell Physiol Biochem. 2016;39:544–553.
   PubMedGoogle Scholar
• De BP, Heguy A, Hackett NR, et al. High Levels of Persistent Expression of α1-Antitrypsin Mediated by the Nonhuman Primate Serotype rh.10 Adeno-associated Virus Despite Preexisting Immunity to Common Human Adeno-associated Viruses. Mol Ther. 2006;13:67–76.
   PubMed Web of Science ®Google Scholar
• Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: new therapies on the horizon. Curr Opin Pharmacol. 2021;59:149–156.
   PubMed Web of Science ®Google Scholar
• Tanash HA, Piitulainen E. Liver disease in adults with severe alpha-1-antitrypsin deficiency. J Gastroenterol. 2019;54:541–548.
   PubMed Web of Science ®Google Scholar
• Zamora MR, Ataya A. Lung and liver transplantation in patients with alpha-1 antitrypsin deficiency. Ther Adv Chronic Dis. 2021;12:20406223211002988.
   Web of Science ®Google Scholar
• Ozaki I, Zern MA, Liu S, et al. Ribozyme-mediated specific gene replacement of the α1-antitrypsin gene in human hepatoma cells. J Hepatol. 1999;31:53–60.
   PubMed Web of Science ®Google Scholar
• Mueller C, Tang Q, Gruntman A, et al. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global Liver miRNA profiles. Mol Ther. 2012;20:590–600.
   PubMed Web of Science ®Google Scholar
• Strnad P, Mandorfer M, Choudhury G, et al. Fazirsiran for liver disease associated with alpha1-antitrypsin deficiency. N Engl J Med. 2022;387:514–524.
   PubMed Web of Science ®Google Scholar
• Song C-Q, Wang D, Jiang T, et al. In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency. Hum Gene Ther. 2018;29:853–860.
   PubMed Web of Science ®Google Scholar
• Ding J, Yannam GR, Roy-Chowdhury N, et al. Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes. J Clin Invest. 2011;121:1930–1934.
   PubMed Web of Science ®Google Scholar
• Borel F, Tang Q, Gernoux G, et al. Survival advantage of both human hepatocyte xenografts and genome-edited hepatocytes for treatment of α-1 antitrypsin deficiency. Mol Ther. 2017;25:2477–2489.
   PubMed Web of Science ®Google Scholar
• Wilson AA, Ying L, Liesa M, et al. Emergence of a stage-dependent human liver disease signature with directed differentiation of Alpha-1 antitrypsin-deficient ips cells. Stem Cell Rep. 2015;4:873–885.
   PubMed Web of Science ®Google Scholar
• Yusa K, Rashid ST, Strick-Marchand H, et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011;478:391–394.
   PubMed Web of Science ®Google Scholar
• Zieger M, Borel F, Greer C, et al. Liver-directed SERPINA1 gene therapy attenuates progression of spontaneous and tobacco smoke-induced emphysema in α1-antitrypsin null mice. Mol Ther - Methods Clin Dev. 2022;25:425–438.
   PubMed Web of Science ®Google Scholar
• Liu P, Liang S-Q, Zheng C, et al. Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice. Nat Commun. 2021;12:2121.
   PubMed Web of Science ®Google Scholar
• He N, Liu X, Vegter AR, et al. Ferret models of alpha-1 antitrypsin deficiency develop lung and liver disease. JCI Insight [Internet]. 2022;7. [cited 2023 Jan 20]. Available from: https://doi.org/10.1172/jci.insight.143004.
   Google Scholar
• McElvaney NG, Burdon J, Holmes M, et al. 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;5:51–60.
   PubMed Web of Science ®Google Scholar
• Chapman KR, Burdon JGW, Piitulainen E, et al. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:360–368.
   PubMed Web of Science ®Google Scholar
• Campos MA, Geraghty P, Holt G, et al. The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial. Am J Respir Crit Care Med. 2019;200:318–326.
   PubMed Web of Science ®Google Scholar