Gene Therapy for Hemophilia: The Clot Thickens

Arruda V.R. , Fields P.A. , Milner R. , et al. (2001). Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males. Mol. Ther., 4, 586–592.

Bedossa P. (1994). Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology, 20, 15–20.

Bi L. , Lawler A.M. , Antonarakis S.E. , et al. (1995). Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat. Genet., 10, 119–121.

Biological Response Modifiers Advisory Committee (2002). Summary Minutes, Meeting #32, May 10, 2002, Gaithersburg, MD. Available at www.fda.gov/OHRMS/DOCKETS/ac/02/minutes/3855m2.pdf (accessed Oct. 10, 2014 ).

Buchlis G. , Podsakoff G.M. , Radu A. , et al. (2012). Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer. Blood, 119, 3038–3041.

Choo K.H. , Gould K.G. , Rees D.J. , and Brownlee G.G . (1982). Molecular cloning of the gene for human anti-haemophilic factor IX. Nature, 299, 178–180.

Chorba T.L. , Holman R.C. , Clarke M.J. , and Evatt B.L . (2001). Effects of HIV infection on age and cause of death for persons with hemophilia A in the United States. Am. J. Hematol., 66, 229–240.

Chu K. , Wu S.M. , Stanley T. , et al. (1996). A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. J. Clin. Invest., 98, 1619–1625.

Darby S.C. , Ewart D.W. , Giangrande P.L. , et al. (1997). Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation. Lancet, 350, 1425–1431.

Evans J.P. , Brinkhous K.M. , Brayer G.D. , et al. (1989a). Canine hemophilia B resulting from a point mutation with unusual consequences. Proc. Natl. Acad. Sci. USA, 86, 10095–10099.

Evans J.P. , Watzke H.H. , Ware J.L. , et al. (1989b). Molecular cloning of a cDNA encoding canine factor IX. Blood, 74, 207–212.

Evatt B.L. (2006). The tragic history of AIDS in the hemophilia population, 1982–1984. J. Thromb. Haemost., 4, 2295–2301.

Evatt B.L. , and Robillard L . (2000). Establishing haemophilia care in developing countries: using data to overcome the barrier of pessimism. Haemophilia, 6, 131–134.

GenStar Therapeutics (2001). GenStar Therapeutics initiates phase i gene therapy clinical trial for hemophilia A gene delivery system utilized for the first time in patients. Available at www.evaluategroup.com/Universal/View.aspx?type=Story&id=15695&sectionID=&isEPVantage=no (accessed October 10, 2014 ).

Giannelli F. , Green P.M. , High K.A. , et al. (1990). Haemophilia B: database of point mutations and short additions and deletions. Nucleic Acids Res., 18, 4053–4059.

Giannelli F. , Green P.M. , Sommer S.S. , et al. (1998). Haemophilia B: database of point mutations and short additions and deletions—eighth edition. Nucleic Acids Res., 26, 265–268.

Gitschier J. , Wood W.I. , Goralka T.M. , et al. (1984). Characterization of the human factor VIII gene. Nature, 312, 326–330.

Herzog R.W. , Hagstrom J.N. , Kung S.H. , et al. (1997). Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc. Natl. Acad. Sci. USA, 94, 5804–5809.

Herzog R.W. , Yang E.Y. , Couto L.B. , et al. (1999). Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat. Med., 5, 56–63.

High K.A. (2012). The gene therapy journey for hemophilia: are we there yet?. Blood, 120, 4482–4487.

High K.A. , and Skinner M.W . (2011). Cell phones and landlines: the impact of gene therapy on the cost and availability of treatment for hemophilia. Mol. Ther., 19, 1749–1750.

Huang M.N. , Kasper C.K. , Roberts H.R. , et al. (1989). Molecular defect in factor IXHilo, a hemophilia Bm variant: Arg–Gln at the carboxyterminal cleavage site of the activation peptide. Blood, 73, 718–721.

Kay M.A. , Manno C.S. , Ragni M.V. , et al. (2000). Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat. Gen., 24, 257–261.

Li C. , Hirsch M. , Asokan A. , et al. (2007a). Adeno-associated virus type 2 (AAV2) capsid-specific cytotoxic T lymphocytes eliminate only vector-transduced cells coexpressing the AAV2 capsid in vivo . J. Virol., 81, 7540–7547.

Li H. , Murphy S.L. , Giles-Davis W. , et al. (2007b). Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Mol. Ther., 15, 792–800.

Lin H.F. , Maeda N. , Smithies O. , et al. (1997). A coagulation factor IX-deficient mouse model for human hemophilia B. Blood, 90, 3962–3966.

Lozier J.N. , Monroe D.M. , Stanfield-Oakley S. , et al. (1990). Factor IX New London: substitution of proline for glutamine at position 50 causes severe hemophilia B. Blood, 75, 1097–1104.

Lozier J.N. , Thompson A.R. , Hu P.C. , et al. (1994). Efficient transfection of primary cells in a canine hemophilia B model using adenovirus-polylysine-DNA complexes. Hum. Gene Ther., 5, 313–322.

Lozier J.N. , Dutra A. , Pak E. , et al. (2002). The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion. Proc. Natl. Acad. Sci. USA, 99, 12991–12996.

Manno C.S. , Chew A.J. , Hutchison S. , et al. (2003). AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood, 101, 2963–2972.

Manno C.S. , Pierce G.F. , Arruda V.R. , et al. (2006). Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med., 12, 342–347.

Massie R.K. (2012). The Romanovs: The Final Chapter. (Random House, New York, NY).

Mingozzi F. , and High K.A . (2011). Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat. Rev. Genet., 12, 341–355.

Mingozzi F. , and High K.A . (2013). Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood, 122, 23–36.

Monroe D.M. , McCord D.M. , Huang M.N. , et al. (1989). Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo. Blood, 73, 1540–1544.

Mount J.D. , Herzog R.W. , Tillson D.M. , et al. (2002). Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy. Blood, 99, 2670–2676.

Murphy S.L. , and High K.A . (2008). Gene therapy for haemophilia. Br. J. Haematol., 140, 479–487.

Nathwani A.C. , Tuddenham E.G.D. , Rangarajan S. , et al. (2011). Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med., 365, 2357–2365.

Osterud B. , and Flengsrud R . (1975). Purification and some characteristics of the coagulation factor IX from human plasma. Biochem. J., 145, 469–474.

Pollak E.S. , and High K.A. (2003). Genetic disorders of coagulation. In Oxford Textbook of Medicine. 4th ed. vol. 3, ch. 22.6.4. Warrell D.A. , Cox T.M. , and Firth J.D. , eds. (Oxford University Press, Inc., New York, NY), pp. 757–767.

Powell J.S. , Ragni M.V. , White G.C. , et al. (2003). Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood, 102, 2038–2045.

Recombinant DNA Advisory Committee (2001). Minutes of Meeting, December 6, 2001. Available at http://osp.od.nih.gov/sites/default/files/Dec01minutes.pdf (accessed Oct. 10, 2014 ).

Recombinant DNA Advisory Committee (2002). Minutes of Meeting, March 7–8, 2002. Available at http://osp.od.nih.gov/sites/default/files/March2002_0.pdf (accessed Oct. 10, 2014 ).

Recombinant DNA Advisory Committee (2007). Immune responses to adeno-associated virus (AAV) vectors: NIH Recombinant DNA Advisory Committee Meeting. Available at http://osp.od.nih.gov/sites/default/files/AAV%20summary%20June%202007f.pdf (accessed Oct 10, 2014 ).

Rogaev E.I. , Grigorenko A.P. , Faskhutdinova G. , et al. (2009). Genotype analysis identifies the cause of the “royal disease.”. Science, 326, 817.

Roth D.A. , Tawa N.E. , O'Brien J.M. , et al. (2001). Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A. N. Engl. J. Med., 344, 1735–1742.

Schuettrumpf J. , Liu J-H. , Couto L.B. , et al. (2006). Inadvertent germline transmission of AAV2 vector: findings in a rabbit model correlate with those in a human clinical trial. Mol. Ther., 13, 1064–1073.

Simioni P. , Tormene D. , Tognin G. , et al. (2009). X-linked thrombophilia with a mutant factor IX (factor IX Padua). N. Engl. J. Med., 361, 1671–1675.

Snyder R.O. , Miao C. , Meuse L. , et al. (1999). Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors. Nat. Med., 5, 64–70.

Wagner B.H. , McLester W.D. , Smith M. , and Brinkhous K.M . (1964). Purification of antihemophilic factor (Factor VIII) by amino acid precipitation. Thromb. Diath. Haemorrh., 11, 64–74.

Walter J. , You Q. , Hagstrom J.N. , et al. (1996). Successful expression of human factor IX following repeat administration of adenoviral vector in mice. Proc. Natl. Acad. Sci. USA, 93, 3056–3061.

Wang L. , Figueredo J. , Calcedo R. , et al. (2007). Cross-presentation of adeno-associated virus serotype 2 capsids activates cytotoxic T cells but does not render hepatocytes effective cytolytic targets. Hum. Gene Ther., 18, 185–194.