Restricted accessResearch articleFirst published online 2014-09
Phase I/II Study of Intrapleural Administration of a Serotype rh.10 Replication-Deficient Adeno-Associated Virus Gene Transfer Vector Expressing the Human α1-Antitrypsin cDNA to Individuals with α1-Antitrypsin Deficiency
AlinoS.F. (1997). Long-term expression of the human alpha1-antitrypsin gene in mice employing anionic and cationic liposome vector. Biochem. Pharmacol., 54, 9–13.
2.
AlinoS.F., BobadillaM., Garcia-SanzM., et al. (1993). In vivo delivery of human alpha 1-antitrypsin gene to mouse hepatocytes by liposomes. Biochem. Biophys. Res. Commun., 192, 174–181.
3.
AlinoS.F., CrespoJ., BobadillaM., et al. (1994). Expression of human alpha 1-antitrypsin in mouse after in vivo gene transfer to hepatocytes by small liposomes. Biochem. Biophys. Res. Commun., 204, 1023–1030.
4.
Alpha-1 Registry. (1998). Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Am. J. Respir. Crit. Care Med., 158, 49–59.
5.
ArmstrongM., MarkL.J., SnyderD.S., ParkerS.D. (1997). Safety of direct laryngoscopy as an outpatient procedure. Laryngoscope, 107, 1060–1065.
6.
ArrudaV.R., SchuettrumpfJ., HerzogR.W., et al. (2004). Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1. Blood, 103, 85–92.
7.
ATS/ERS Task Force. (2003). American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med., 168, 818–900.
8.
BaoJ.J., SifersR.N., KiddV.J., et al. (1987). Molecular evolution of serpins: homologous structure of the human alpha 1-antichymotrypsin and alpha 1-antitrypsin genes. Biochemistry, 26, 7755–7759.
9.
BirrerP., McElvaneyN.G., Chang-StromanL.M., and CrystalR.G. (1991). Alpha 1-antitrypsin deficiency and liver disease. J. Inherit. Metab. Dis., 14, 512–525.
10.
BrantlyM., NukiwaT., and CrystalR.G. (1988). Molecular basis of alpha-1-antitrypsin deficiency. Am. J. Med., 84, 13–31.
11.
BrantlyM.L., WittesJ.T., VogelmeierC.F., et al. (1991). Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes. Chest, 100, 703–708.
12.
BrantlyM.L., SpencerL.T., HumphriesM., et al. (2006). Phase I trial of intramuscular injec-tion of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum. Gene Ther., 17, 1177–1186.
13.
BrantlyM.L., ChulayJ.D., WangL., et al. (2009). Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc. Natl. Acad. Sci. USA, 106, 16363–16368.
14.
BrighamK.L., LaneK.B., MeyrickB., et al. (2000). Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum. Gene Ther., 11, 1023–1032.
15.
BrodyS.L., MetzgerM., DanelC., et al. (1994). Acute responses of non-human primates to airway delivery of an adenovirus vector containing the human cystic fibrosis transmembrane conductance regulator cDNA. Hum. Gene Ther., 5, 821–836.
16.
CanonicoA.E., ConaryJ.T., MeyrickB.O., and BrighamK.L. (1994a). Aerosol and intravenous transfection of human alpha 1-antitrypsin gene to lungs of rabbits. Am. J. Respir. Cell Mol. Biol., 10, 24–29
17.
CanonicoA.E., PlitmanJ.D., ConaryJ.T., et al. (1994b). No lung toxicity after repeated aerosol or intravenous delivery of plasmid-cationic liposome complexes. J. Appl. Physiol., 77, 415–419
18.
CanonicoA.E., BrighamK.L., CarmichaelL.C., et al. (1996). Plasmid-liposome transfer of the alpha 1 antitrypsin gene to cystic fibrosis bronchial epithelial cells prevents elastase-induced cell detachment and cytokine release. Am. J. Respir. Cell Mol. Biol., 14, 348–355.
19.
CarrellR.W., and LomasD.A. (2002). Alpha1-antitrypsin deficiency-a model for conformational diseases. N. Engl. J. Med., 346, 45–53.
20.
ChiuchioloM.J., KaminskyS.M., SondhiD., et al. (2013). Intrapleural administration of an AAVrh.10 vector coding for human α1-antitrypsin for the treatment of α1-antitrypsin deficiency. Hum. Gene Ther. Clin. Dev., 24, 161–173.
21.
ChulayJ.D., YeG.J., ThomasD.L., et al. (2011). Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method. Hum. Gene Ther., 22, 155–165.
22.
CohenA.B., WooS., KelleyR., et al. (1988). Molecular genetics in pulmonary emphysema. Am. Rev. Respir. Dis., 138, 1041–1043.
23.
CoxD.W., WooS.L., and MansfieldT. (1985). DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z. Nature, 316, 79–81.
24.
CrepsoJ., BlayaC., CrespoA., and AlinoS.F. (1996). Long-term expression of the human alpha1-antitrypsin gene in mice employing anionic and cationic liposome vectors. Biochem. Pharmacol., 51, 1309–1314.
25.
CrystalR.G. (1989). The alpha 1-antitrypsin gene and its deficiency states. Trends Genet., 5, 411–417.
26.
CrystalR.G. (1990). Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J. Clin. Invest., 85, 1343–1352.
CrystalR.G., BrantlyM.L., HubbardR.C., et al. (1989). The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy. Chest, 95, 196–208.
29.
CurielD.T., VogelmeierC., HubbardR.C., et al. (1990). Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele. Mol. Cell Biol., 10, 47–56.
30.
DeB., HeguyA., LeopoldP.L., et al. (2004a). Intrapleural administration of a serotype 5 adeno-associated virus coding for alpha1-antitrypsin mediates persistent, high lung and serum levels of alpha1-antitrypsin. Mol. Ther., 10, 1003–1010
31.
DeS.A., VanderlindenE., DemanetC., et al. (2004b). Characterisation of pleural inflammation occurring after primary spontaneous pneumothorax. Eur. Respir. J., 23, 896–900
32.
DeB.P., HeguyA., HackettN.R., et al. (2006). High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol. Ther., 13, 67–76.
33.
de SerresF.J. (2002). Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys. Chest, 122, 1818–1829.
34.
DirksenA., DijkmanJ.H., MadsenF., et al. (1999). A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am. J. Respir. Crit. Care Med., 160, 1468–1472.
35.
FerrariS., GeddesD.M., and AltonE.W. (2002). Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis. Adv. Drug Deliv. Rev., 54, 1373–1393.
36.
FerrariS., GriesenbachU., GeddesD.M., and AltonE. (2003). Immunological hurdles to lung gene therapy. Clin. Exp. Immunol., 132, 1–8.
37.
FlotteT.R., and MuellerC. (2011). Gene therapy for alpha-1 antitrypsin deficiency. Hum. Mol. Genet., 20, R87–R92.
38.
FlotteT.R., TrapnellB.C., HumphriesM., et al. (2011). Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results. Hum. Gene Ther., 22, 1239–1247.
39.
GadekJ., and CrystalR.G. (1982). Alpha-1-antitrypsin deficiency. In Metabolic Basis of Inherited Disease. StanburyJ.B., WyngaardenJ.B., FredericksonD.S., et al., eds. (McGrawHill, New York, NY) pp. 1450–1467.
40.
GadekJ.E., FellsG.A., ZimmermanR.L., et al. (1981). Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. J. Clin. Invest., 68, 889–898.
41.
GaoG., VandenbergheL.H., and WilsonJ.M. (2005). New recombinant serotypes of AAV. Curr. Gene Ther., 5, 285–297.
42.
GarverR.I.Jr., ChytilA., CourtneyM., and CrystalR.G. (1987). Clonal gene therapy: in vivo expression of a transplanted monoclonal population of murine fibroblasts containing a retrovirus inserted human alpha 1-antitrypsin gene. Trans. Assoc. Am. Phys., 100, 10–20.
43.
GreeneC.M., MillerS.D., CarrollT., et al. (2008). Alpha-1 antitrypsin deficiency: a conformational disease associated with lung and liver manifestations. J. Inherit. Metab. Dis., 31, 21–34.
44.
HarveyB.G., HackettN.R., El SawyT., et al. (1999a). Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs. J. Virol., 73, 6729–6742
45.
HarveyB.G., LeopoldP.L., HackettN.R., et al. (1999b). Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus. J. Clin. Invest., 104, 1245–1255
46.
HarveyB.G., HackettN.R., ElyS., and CrystalR.G. (2001). Host responses and persistence of vector genome following intrabronchial administration of an E1(-)E3(-) adenovirus gene transfer vector to normal individuals. Mol. Ther., 3, 206–215.
47.
HighK. (2002a). AAV-mediated gene transfer for hemophilia. Genet. Med., 4, 56S–61S
48.
HighK.A. (2002b). Adeno-associated virus-mediated gene transfer for hemophilia B. Int. J. Hematol., 76, 310–318
49.
HighK.A. (2004). Clinical gene transfer studies for hemophilia B. Semin. Thromb. Hemost., 30, 257–267.
50.
HubbardR.C., and CrystalR.G. (1990). Augmentation therapy of alpha 1-antitrypsin deficiency. Eur. Respir. J. Suppl., 9, 44s–52s.
51.
HubbardR.C., SellersS., CzerskiD., et al. (1988). Biochemical efficacy and safety of monthly augmentation therapy for alpha 1-antitrypsin deficiency. JAMA, 260, 1259–1264.
52.
JaffeH.A., DanelC., LongeneckerG., et al. (1992). Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. Nat. Genet., 1, 372–378.
53.
JonesE.A., VergallaJ., SteerC.J., et al. (1978). Metabolism of intact and desialylated alpha 1-antitrypsin. Clin. Sci. Mol. Med., 55, 139–148.
54.
KatzensteinA.L., BloorC.M., and LeibowA.A. (1976). Diffuse alveolar damage—the role of oxygen, shock, and related factors. A review. Am. J. Pathol., 85, 209–228.
55.
KatzensteinA.L., MyersJ.L., and MazurM.T. (1986). Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. Am. J. Surg. Pathol., 10, 256–267.
56.
KayM.A., BaleyP., RothenbergS., et al. (1992). Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. Proc. Natl. Acad. Sci. USA, 89, 89–93.
57.
LarsonP.J., and HighK.A. (2001). Gene therapy for hemophilia B: AAV-mediated transfer of the gene for coagulation factor IX to human muscle. Adv. Exp. Med. Biol., 489, 45–57.
58.
LaurellC.B., and ErikssonS.E. (1963). The electrophoretic alpha-globulin pattern of serum in alpha-antitrypsin deficiency. Scand. J. Clin. Invest., 15, 132–140.
59.
LevyM.Y., BarronL.G., MeyerK.B., and SzokaF.C.Jr. (1996). Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Ther., 3, 201–211.
60.
LightR.W. (2001). Physiology of the pleural space. In Pleural Diseases. LightR.W., ed. (Lippincott Williams & Wilkins, Philadelphia, PA) pp. 8–20.
61.
LimberisM.P., VandenbergheL.H., ZhangL., et al. (2009). Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro. Mol. Ther., 17, 294–301.
62.
LiuY.L., MingozziF., Rodriguez-ColonS.M., et al. (2004). Therapeutic levels of factor IX expression using a muscle-specific promoter and adeno-associated virus serotype 1 vector. Hum. Gene Ther., 15, 783–792.
63.
LoebermannH., TokuokaR., DeisenhoferJ., and HuberR. (1984). Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J. Mol. Biol., 177, 531–557.
LomasD.A., EvansD.L., FinchJ.T., et al. (1992). The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature, 357, 605–607.
66.
LongG.L., ChandraT., WooS.L., et al. (1984). Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant. Biochemistry, 23, 4828–4837.
67.
LuY., Campbell-ThompsonM., LiC., et al. (2004) Functional human alpha 1 antitrypsin secreted from muscle transduced by adeno-associated virus (rAAV1) vector. Mol. Ther., 9, S41–S42.
68.
LuY., ChoiY.K., Campbell-ThompsonM., et al. (2006). Therapeutic level of functional hu-man alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector. J. Gene Med., 8, 730–735.
69.
LuisettiM., MiravitllesM., and StockleyR.A. (2002). Alpha l-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001. Eur. Respir. J., 20, 1050–1056.
70.
MaeM., and CrystalR.G. (2002). Gene transfer to the pleural mesothelium as a strategy to deliver proteins to the lung parenchyma. Hum. Gene Ther., 13, 1471–1482.
71.
MannoC.S., ChewA.J., HutchisonS., et al. (2003). AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood, 101, 2963–2972.
72.
MastrangeliA., HarveyB.G., and YaoJ. (1996). “Sero-switch” adenovirus-mediated in vivo gene transfer: circumvention of anti-adenovirus humoral immune defenses against repeat adenovirus vector administration by changing the adenovirus serotype. Hum. Gene Ther., 7, 79–87.
MomexJ.F., Chytil-WeirA., MartinetY., et al. (1986). Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals. J. Clin. Invest., 77, 1952–1961.
75.
MuellerC., and FlotteT.R. (2013). Gene-based therapy for alpha-1 antitrypsin deficiency. COPD, 10Suppl 1, 44–49.
76.
MullinsC.D., HuangX., MerchantS., and StollerJ.K. (2001). The direct medical costs of alpha(l)-antitrypsin deficiency. Chest, 119, 745–752.
77.
MyersJ.L., and KatzensteinA.L. (1988). Ultrastructural evidence of alveolar epithelial injury in idiopathic bronchiolitis obliterans-organizing pneumonia. Am. J. Pathol., 132, 102–109.
78.
OgushiF., FellsG.A., HubbardR.C., et al. (1987). Z-type alpha 1-antitrypsin is less competent than M1-type alpha 1-antitrypsin as an inhibitor of neutrophil elastase. J. Clin. Invest., 80, 1366–1374.
79.
OgushiF., HubbardR.C., VogelmeierC., et al. (1991). Risk factors for emphysema. Cigarette smoking is associated with a reduction in the association rate constant of lung alpha 1-antitrypsin for neutrophil elastase. J. Clin. Invest., 87, 1060–1065.
80.
PertmerT.M., EisenbraunM.D., McCabeD., et al. (1995). Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine, 13, 1427–1430.
81.
QiuP., ZiegelhofferP., SunJ., and YangN.S. (1996). Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization. Gene Ther., 3, 262–268.
82.
RennardS.I., BassetG., LecossierD., et al. (1986). Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J. Appl. Physiol., 60, 532–538.
83.
RosenfeldM.A., SiegfriedW., YoshimuraK., et al. (1991). Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science, 252, 431–434.
84.
RosenfeldM.A., YoshimuraK., TrapnellB.C., et al. (1992). In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell, 68, 143–155.
85.
RosenfeldM.A., RonaldG., and CrystalR.G. (1993). Gene therapy for pulmonary diseases. Pathol. Biol. (Paris), 41, 677–680.
86.
SchreierH., GagneL., BockT., et al. (1997). Physicochemical properties and in vitro toxicity of cationic liposome cDNA complexes. Pharm. Acta Helv., 72, 215–223.
87.
SchroederW.T., MillerM.F., WooS.L., and SaundersG.F. (1985). Chromosomal localization of the human alpha 1-antitrypsin gene (PI) to 14q31-32. Am. J. Hum. Genet., 37, 868–872.
88.
SeixasS., GarciaO., TrovoadaM.J., et al. (2001). Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism. Hum. Genet., 108, 20–30.
89.
SetoguchiY., JaffeH.A., ChuC.S., and CrystalR.G. (1994). Intraperitoneal in vivo gene therapy to deliver alpha 1-antitrypsin to the systemic circulation. Am. J. Respir. Cell Mol. Biol., 10, 369–377.
90.
SilvermanE.K., and SandhausR.A. (2009). Clinical practice. Alpha1-antitrypsin deficiency. N. Engl. J. Med., 360, 2749–2757.
91.
SongS., MorganM., EllisT., et al. (1998) Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. USA, 95, 14384–14388.
92.
SongS., EmburyJ., LaipisP.J., et al. (2001). Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors. Gene Ther., 8, 1299–1306.
93.
SongS., Scott-JorgensenM., WangJ., et al. (2002). Intramuscular administration of recombinant adeno-associated virus 2 alpha-1 antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: safety and immunologic aspects. Mol. Ther., 6, 329–335.
94.
StecenkoA.A., and BrighamK.L. (2003). Gene therapy progress and prospects: alpha-1 antitrypsin. Gene Ther., 10, 95–99.
95.
StockleyR.A. (2000). Alpha-1-antitrypsin deficiency: what next?. Thorax, 55, 614–618.
96.
StocksJ.M., BrantlyM.L., Wang-SmithL., et al. (2010). Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha-antitrypsin deficiency: a randomized study. BMC Clin. Pharmacol., 30, 10–13.
97.
StollerJ.K., and AboussouanL.S. (2005). Alpha1-antitrypsin deficiency. Lancet, 365, 2225–2236.
98.
StollerJ.K., and AboussouanL.S. (2012). A review of alpha1-antitrypsin deficiency. Am. J. Respir. Crit. Care Med., 185, 246–259.
99.
StrangeP. (2001). Pleural diseases. In Egan's Fundamentals of Respiratory Care. ScanlanC.L., WilkinsR.L., and StollerJ.K., eds. (Elsevier Inc., St. Louis, MO) pp. 475–490.
100.
TeramotoS., BartlettJ.S., McCartyD., et al. (1998). Factors influencing adeno-associated virus-mediated gene transfer to human cystic fibrosis airway epithelial cells: comparison with adenovirus vectors. J. Virol., 72, 8904–8912.
101.
Thompson Healthcare (2010). Red Book: Pharmacy's Fundamental Reference. (Thomson Reuters, PDR Network, New York).
102.
TuderR.M., JanciauskieneS.M., and PetracheI. (2010). Lung disease associated with alpha1-antitrypsin deficiency. Proc. Am. Thorac. Soc., 7, 381–386.
103.
VadolasJ., WilliamsonR., and IoannouP.A. (2002). Gene therapy for inherited lung disorders: an insight into pulmonary defence. Pulm. Pharmacol. Ther., 15, 61–72.
104.
Virella-LowellI., PoirierA., ChesnutK.A., et al. (2000). Inhibition of recombinant adeno-associated virus (rAAV) transduction by bronchial secretions from cystic fibrosis patients. Gene Ther., 7, 1783–1789.
105.
WewersM.D., CasolaroM.A., and CrystalR.G. (1987). Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy. Am. Rev. Respir. Dis., 135, 539–543.
106.
WuS.S., de ChadarevianJ.P., McPhaulL., et al. (2002). Coexpression and accumulation of ubiquitin+1 and ZZ proteins in livers of children with alpha-1 antitrypsin deficiency. Pediatr. Dev. Pathol., 5, 293–298.
107.
YangY., LiQ., ErtlH.C., et al. (1995). Cellular and humoral immune responses to viral anti-gens create barriers to lung-directed gene therapy with recombinant adenoviruses. J. Virol., 69, 2004–2015.
108.
ZamoraN.P., PlaR.V., Del RioP.G., et al. (2008). Intravenous human plasma-derived augmentation therapy in alpha 1-antitrypsin deficiency: from pharmacokinetic analysis to individualizing therapy. Ann. Pharmacother., 42, 640–646.