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Expert Opinion on Biological Therapy Volume 16, 2016 - Issue 1
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Reviews

New and improved AAVenues: current status of hemophilia B gene therapy

Mark A BrimbleDepartment of Haematology, University College London Cancer Institute, LondonWC1E 6DD, UK;Department of Surgery, St Jude Children’s Research Hospital, Memphis, TN38105, USA
,
Ulrike M ReissClinical Haematology, St Jude Children’s Research Hospital, Memphis, TN38105, USA
,
Amit C NathwaniDepartment of Haematology, University College London Cancer Institute, LondonWC1E 6DD, UK;Katherine Dormandy Haemophilia and Thrombosis Unit, Royal Free NHS Foundation Trust, LondonNW3 2QG, UK;Oak House Reeds Crescent, NHS, Blood And Transplant, WatfordWD24 4QN, UK
&
Andrew M DavidoffDepartment of Surgery, St Jude Children’s Research Hospital, Memphis, TN38105, USACorrespondence[email protected]
Pages 79-92 | Published online: 02 Nov 2015

References

  • Papers of special note have been highlighted as either of interest (*) or of considerable interest
  • (**) to readers.
  • Mannucci P, Tuddenham EG. The hemophilias — from royal genes to gene therapy. N Engl J Med. 2001;344(23):1773–1779.
  • Rallapalli PM, Kemball-Cook G, Tuddenham EG, et al. An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B. J Thromb Haemost. 2013;11(7):1329–1340. DOI:10.1111/jth.12276.
  • Keeling D, Tait C, Markis M. Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia. 2008;14:671–684. DOI:10.1111/j.1365-2516.2008.01695.x.
  • Manco-Johnson M, Abshire T, Shipiro A, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535–544.
  • Kempton CL, White GC II. How we treat a hemophilia A patient with a factor VIII inhibitor. Blood. 2015;113(1):11–18. DOI:10.1182/blood-2008-06-160432.
  • Dimichele D. Inhibitor development in haemophilia B : an orphan disease in need of attention. Br J Haematol. 2007;138:305–315. DOI:10.1111/j.1365-2141.2007.06657.x.
  • Schrijvers LH, Uitslager N, Schuurmans MJ, et al. Barriers and motivators of adherence to prophylactic treatment in haemophilia: a systematic review. Haemophilia. 2013;19(3):355–361. DOI:10.1111/hae.12079.
  • Guh S, Grosse SD, McAlister S, et al. Healthcare expenditures for males with haemophilia and employer-sponsored insurance in the United States, 2008. Haemophilia. 2012;18(2):268–275. DOI:10.1111/j.1365-2516.2011.02692.x.
  • Petrini P. Identifying and overcoming barriers to prophylaxis in the management of haemophilia. Haemophilia. 2007;13(Suppl. 2):16–22. DOI:10.1111/j.1365-2516.2007.01501.x.
  • Kurachi K, Davie EW. Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci U S A. 1982;79(21):6461–6464.
  • Lheriteau E, Davidoff AM, Nathwani AC. Haemophilia gene therapy: progress and challenges. Blood Rev. 2015. DOI:10.1016/j.blre.2015.03.002.
  • Bolton-Maggs PHB, Pasi KJ. Haemophilias A and B. Lancet. 2003;361(9371):1801–1809. DOI:10.1016/S0140-6736(03)13405-8.
  • Valentino LA. Recombinant FIXFc : a novel therapy for the royal disease ? Expert Opin Biol Ther. 2011;11(10):1361–1368.
  • Hacein-Bey-Abina S, Le Deist F, Carlier F, et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med. 2002;346(16):1185–1193.
  • Xu L, Gao C, Sands MS, et al. Neonatal or hepatocyte growth factor – potentiated adult gene therapy with a retroviral vector results in therapeutic levels of canine factor IX for hemophilia B. Blood. 2003;101(10):3924–3932. DOI:10.1182/blood-2002-10-3050.
  • Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348(3):255–256. DOI:10.1056/NEJM200301163480314.

** The clinical trial update detailing the first leukemogenic events as a result of retroviral gene therapy, resulting in a halt on all retroviral trials.

  • Hacein-Bey-Abina S, Hauer J, Lim A, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363(4):355–364. DOI:10.1056/NEJMoa1000164.
  • Marwick C. FDA halts gene therapy trialsafter leukemia case in France. BMJ. 2003;326(7382):181.
  • Penaud-Budloo M, Le Guiner C, Nowrouzi A, et al. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol. 2008;82(16):7875–7885. DOI:10.1128/JVI.00649-08.
  • Qui X, Lu D, Zhou J, et al. Implantation of autologous skin fibroblast genetically modified to secrete clotting factor IX partially corrects the hemorrhagictendencies in two hemophilia B patients. Chin Med J (Engl). 1996;109(11):832–839. DOI:10.1016/j.biotechadv.2011.08.021.

* The first ever gene therapy trial for hemophilia B. The partial correction from skin fibroblasts provided a basis to propose that gene transfer could be a successful modality for hemophilia B.

  • Herzog RW, Yang EY, Couto LB, et al. Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat Med. 1999;5(1):56–63. DOI:10.1038/4743.
  • Manno CS, Chew AJ, Hutchison S, et al. AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood. 2003;101(8):2963–2972. DOI:10.1182/blood-2002-10-3296.
  • Kay MA, Manno CS, Ragni MV, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet. 2000;24(March):257–261.
  • Jiang H, Pierce GF, Ozelo MC, et al. Evidence of multiyear factor IX expression by AAV-mediated gene transfer to skeletal muscle in an individual with severe hemophilia B. Mol Ther. 2006;14(3):452–455. DOI:10.1016/j.ymthe.2006.05.004.
  • Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342–347. DOI:10.1038/nm1358.
  • Nathwani AC, Tuddenham EGD, Rangarajan S, et al. Adeno-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–2365.

** The University College London/St Jude Children’s Research Hospital (UCL/SJCRH) clinical trial paper, showing the first sustained correction of the hemophilia B bleeding phenotype.

  • Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004. DOI:10.1056/NEJMoa1407309.

* An update on the UCL/SJCRH trial, showing sustained expression from adeno-associated virus (AAV) gene transfer at around 4 years post-gene transfer.

  • Atchison R, Casto B, Hammon W. Adenovirus-associated defective virus particles. Science. 1965;149(3685):754–756.
  • Grossman Z, Mendelson E, Mileguir F, et al. Detection of adeno-associated virus type 2 in human peripheral blood cells. J Gen Virol. 1992;7374:961–966.
  • Davidoff AM, Ng CYC, Zhou J, et al. Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway. Blood. 2003;102(2):480–488. DOI:10.1182/blood-2002-09-2889.
  • Salmon F, Grosios K, Petry H. Safety profile of recombinant adeno-associated viral vectors: focus on alipogene tiparvovec (Glybera(®)). Expert Rev Clin Pharmacol. 2014;7:53–65. DOI:10.1586/17512433.2014.852065.
  • Daya S, Berns KI. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev. 2008;21(4):583–593. DOI:10.1128/CMR.00008-08.
  • Nowrouzi A, Penaud-Budloo M, Kaeppel C, et al. Integration frequency and intermolecular recombination of rAAV vectors in non-human primate skeletal muscle and liver. Mol Ther. 2012;20(6):1177–1186. DOI:10.1038/mt.2012.47.
  • Bowles DE, McPhee SWJ, Li C, et al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012;20(2):443–455. DOI:10.1038/mt.2011.237.
  • Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240–2248. DOI:10.1056/NEJMoa0802315.
  • Moss RB, Milla C, Colombo J, et al. Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis : a randomized placebo-controlled phase 2B trial. Hum Gene Ther. 2007;732(August):726–732. DOI:10.1089/hum.2007.022.
  • Zincarelli C, Soltys S, Rengo G, et al. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16(6):1073–1080. DOI:10.1038/mt.2008.76.
  • Petrs-Silva H, Dinculescu A, Li Q, et al. High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther. 2009;17(3):463–471. DOI:10.1038/mt.2008.269.
  • Askew C, Rochat C, Pan B, et al. Tmc gene therapy restores auditory function in deaf mice. Sci Transl Med. 2015;7(295):1–12.
  • Hentzschel F, Hammerschmidt-Kamper C, Börner K, et al. AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites. Mol Ther. 2014;22(12):2130–2141. DOI:10.1038/mt.2014.172.
  • Franich NR, Fitzsimons HL, Fong DM, et al. AAV vector-mediated RNAi of mutant huntingtin expression is neuroprotective in a novel genetic rat model of Huntington’s disease. Mol Ther. 2008;16(5):947–956. DOI:10.1038/mt.2008.50.
  • Denbo JW, Williams RF, Orr WS, et al. Continuous local delivery of interferon- b stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model. Surgery. 2011;150(3):497–504. DOI:10.1016/j.surg.2011.07.044.
  • Nakai H, Fuess S, Storm TA, et al. Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice. J Virol. 2005;79(1):214–224. DOI:10.1128/JVI.79.1.214-224.2005.
  • Thomas CE, Storm TA, Huang Z, et al. Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectors. J Virol. 2004;78(6):3110–3122. DOI:10.1128/JVI.78.6.3110-3122.2004.
  • Nathwani AC, Gray JT, McIntosh J, et al. Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood. 2007;109(4):1414–1421. DOI:10.1182/blood-2006-03-010181.
  • Nathwani AC, Rosales C, Mcintosh J, et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther. 2011;19(5):876–885. DOI:10.1038/mt.2010.274.

* Preclinical data from macaques that show the long-term safety of systemic injection of several AAV serotypes.

  • Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1,2,5,6,8, and 9 in the healthy population : implications for gene therapy using AAV vectors. Hum Gene Ther. 2010;712(June):704–712.
  • Hirata RK, Russell DW. Design and packaging of adeno-associated virus gene targeting vectors. J Virol. 2000;74(10):4612–4620. DOI:10.1128/JVI.74.10.4612-4620.2000.
  • McCarty DM, Fu H, Monahan PE, et al. Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther. 2003;10(26):2112–2118. DOI:10.1038/sj.gt.3302134.
  • McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 2001;8(16):1248–1254. DOI:10.1038/sj.gt.3301514.

* This paper details the construction and enhanced transduction of self-complimentary AAV vectors, which have proven valuable for driving strong transgene expression in the clinical setting.

  • Simioni P, Tormene D, Tognin G, et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N Engl J Med. 2009;361(17):1671–1675. DOI:10.1056/NEJMoa0904377.
  • Finn JD, Nichols TC, Svoronos N, et al. The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy. Blood. 2012;120(23):4521–4523. DOI:10.1182/blood-2012-06-440123.
  • Cantore A, Nair N, Della Valle P, et al. Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice. Blood. 2015;120(23):4517–4521. DOI:10.1182/blood-2012-05-432591.
  • Crudele JM, Finn JD, Siner JI, et al. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood. 2015;125(10):1553–1562. DOI:10.1182/blood-2014-07-588194.
  • Press-Release. Baxalta reports continued progress on Phase 1/2 clinical trial of BAX335, investigational aene therapy treatment for Hemophilia B. Reuters. 2015 [cited 2015 Aug 8]. Available from: www.reuters.com/article/2015/06/24/il-baxalta-incorporated-idUSnBw245677a+100+BSW20150624.
  • Liu Q, Huang W, Zhang H, et al. Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Ther. 2014;21(8):732–738. DOI:10.1038/gt.2014.47.
  • Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis. 2009;199(3):381–390. DOI:10.1086/595830.

* A worldwide examination of the prevalence of Nabs to AAV, highlighting a significant barrier to expanding gene therapy treatment globally.

  • Calcedo R, Morizono H, Wang L, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol. 2011;18(9):1586–1588. DOI:10.1128/CVI.05107-11.
  • Knobe K, Berntorp E. Haemophilia and joint disease : pathophysiology, evaluation, and management. J Comormidity. 2011;1(1):51–59.
  • Iorio A, Marchesini E, Marcucci M, et al. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. 2011;9(9):CD003429. DOI:10.1002/14651858.CD003429.pub3.
  • Wu T-L, Li H, Faust SM, et al. CD8(+) T cell recognition of epitopes within the capsid of adeno-associated virus 8-based gene transfer vectors depends on vectors’ genome. Mol Ther. 2014;22(1):42–51. DOI:10.1038/mt.2013.218.
  • Parzych EM, Li H, Yin X, et al. Effects of immunosuppression on circulating adeno-associated virus capsid-specific T cells in humans. Hum Gene Ther. 2013;24(4):431–442. DOI:10.1089/hum.2012.246.
  • Unzu C, Hervás-Stubbs S, Sampedro A, et al. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates. J Transl Med. 2012;10(1):122. DOI:10.1186/1479-5876-10-122.
  • Hui DJ, Basner-Tschakarjan E, Chen Y, et al. Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes. Mol Ther. 2013;21(9):1727–1737. DOI:10.1038/mt.2013.166.
  • Thompson AG, Thomas R. Induction of immune tolerance by dendritic cells: implications for preventative and therapeutic immunotherapy of autoimmune disease. Immunol Cell Biol. 2002;80(6):509–519. DOI:10.1046/j.1440-1711.2002.01114.x.
  • Larrubia JR, Moreno-cubero E, Lokhande MU, et al. Adaptive immune response during hepatitis C virus infection. World J Gastroenterol. 2014;20(13):3418–3430. DOI:10.3748/wjg.v20.i13.3418.
  • Herzog RW. Hepatic AAV gene transfer and the immune system: friends or foes? Mol Ther. 2010;18(6):1063–1066. DOI:10.1038/mt.2010.96.
  • LoDuca PA, Hoffman BE, Herzog RW. Hepatic gene transfer as a means of tolerance induction to transgene products. Curr Gene Ther. 2009;9(2):104–114. DOI:10.2174/156652309787909490.
  • Mingozzi F, Chen Y, Murphy SL, et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther. 2012;20(7):1410–1416. DOI:10.1038/mt.2012.84.
  • Gao G, Wang Q, Calcedo R, et al. Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Hum Gene Ther. 2009;20(9):930–942. DOI:10.1089/hum.2009.060.
  • Rutledge EA, Halbert CL, Russell DW. Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J Virol. 1998;72(1):309–319.
  • Rabinowitz JE, Samulski RJ. Building a better vector: the manipulation of AAV virions. Virology. 2000;278(2):301–308. DOI:10.1006/viro.2000.0707.
  • Wu Z, Asokan A, Samulski RJ. Adeno-associated virus serotypes : vector toolkit for human gene therapy. Mol Ther. 2006;14(3):316–327. DOI:10.1016/j.ymthe.2006.05.009.
  • Kotterman MA, Schaffer DV. Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet. 2014;15(7):445–451. DOI:10.1038/nrg3742.

** Comprehensive review of efforts to engineer AAV vectors with new properties.

  • Maguire CA, Gianni D, Meijer DH, et al. Directed evolution of adeno-associated virus for glioma cell transduction. J Neurooncol. 2010;96:337–347. DOI:10.1007/s11060-009-9972-7.
  • Adachi K, Enoki T, Kawano Y, et al. Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing. Nat Commun. 2014;5:3075. DOI:10.1038/ncomms4075.
  • Grimm D, Lee JS, Wang L, et al. In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses. J Virol. 2008;82(12):5887–5911. DOI:10.1128/JVI.00254-08.
  • Zinn E, Pacouret S, Khaychuk V, et al. In silico reconstruction of the viral evolutionary lineage yields a potent gene therapy vector. Cell Rep. 2015:1–13. DOI:10.1016/j.celrep.2015.07.019.
  • Lisowski L, Dane AP, Chu K, et al. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. Nature. 2014;506(7488):382–386. DOI:10.1038/nature12875.

* A new in vivo AAV selection method that resulted in a very strong hepatic gene therapy serotype candidate LK03.

  • Martino AT, Basner-Tschakarjan E, Markusic DM, et al. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells. Blood. 2013;121(12):2224–2233. DOI:10.1182/blood-2012-10-460733.
  • Halbert CL, Rutledge EA, Allen JM, et al. Repeat transduction in the mouse lung by using adeno-associated virus vectors with different serotypes. J Virol. 2000;74(3):1524–1532. DOI:10.1128/JVI.74.3.1524-1532.2000.
  • Lochrie MA, Tatsuno GP, Christie B, et al. Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. J Virol. 2006;80(2):821–834. DOI:10.1128/JVI.80.2.821.
  • Harbison CE, Weichert WS, Gurda BL, et al. Examining the cross-reactivity and neutralization mechanisms of a panel of mabs against adeno-associated virus serotypes 1 and 5. J Gen Virol. 2012;93(2):347–355. DOI:10.1099/vir.0.035113-0.
  • Chen Y, Schroeder JA, Kuether EL, et al. Platelet gene therapy by lentiviral gene delivery to hematopoietic stem cells restores hemostasis and induces humoral immune tolerance in FIXnull mice. Mol Ther. 2013;22(1):169–177. DOI:10.1038/mt.2013.197.
  • Chang AH, Stephan MT, Sadelain M. Stem cell-derived erythroid cells mediate long-term systemic protein delivery. Nat Biotechnol. 2006;24(8):1017–1021. DOI:10.1038/nbt1227.
  • Sun J, Hakobyan N, Valentino LA, et al. Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX. Blood. 2008;112(12):4532–4541. DOI:10.1182/blood-2008-01-131417.
  • Ran FA, Cong L, Yan WX, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015. DOI:10.1038/nature14299.
  • Li H, Haurigot V, Doyon Y, et al. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature. 2011;475(7355):217–221. DOI:10.1038/nature10177.
  • Anguela XM, Sharma R, Doyon Y, et al. Robust ZFN-mediated genome editing in adult hemophilic mice. Blood. 2013;122(19):3283–3287. DOI:10.1182/blood-2013-04-497354.
  • Barzel A, Paulk NK, Shi Y, et al. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2014;517(7534):360–364. DOI:10.1038/nature13864.

** A new method of correcting hemophilia B through AAV delivery to the liver, resulting in a permanent, targeted and expressed genomic insertion of the transgene.

  • Monahan PE. Gene therapy in an era of emerging treatment options for hemophilia B. J Thromb Haemost. 2015;13:151–160. DOI:10.1111/jth.12957.
  • Metzner HJ, Pipe SW, Weimer T, et al. Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin. Thromb Haemost. 2013;110(5):931–939. DOI:10.1160/TH13-03-0213.
  • Verma D, Moghimi B, LoDuca PA, et al. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. Proc Natl Acad Sci U S A. 2010;107(15):7101–7106. DOI:10.1073/pnas.0912181107.
  • Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia. 2006;12(Suppl. 6):15–22. DOI:10.1111/j.1365-2516.2006.01361.x.

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