Gene therapy in a humanized mouse model of familial hypercholesterolemia leads to marked regression of atherosclerosis

PLoS ONE

Volumn 5, Issue 10, 2010, Pages

  Kassim, Sadik H ^a   Li, Hui ^b   Vandenberghe, Luk H ^a   Hinderer, Christian ^a   Bell, Peter ^a   Marchadier, Dawn ^b   Wilson, Aisha ^b   Cromley, Debra ^b   Redon, Valeska ^b   Yu, Hongwei ^a   Wilson, James M ^a   Rader, Daniel J ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; PARVOVIRUS VECTOR; VERY LOW DENSITY LIPOPROTEIN RECEPTOR; PRIMER DNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; FAMILIAL HYPERCHOLESTEROLEMIA; MALE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; REMISSION; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; ANIMAL; C57BL MOUSE; DISEASE MODEL; GENE THERAPY; GENETICS; HUMAN; HYPERLIPOPROTEINEMIA TYPE 2; IMMUNOHISTOCHEMISTRY;

ADENO-ASSOCIATED VIRUS - 8; ANIMALIA; MUS;

ANIMALS; ATHEROSCLEROSIS; BASE SEQUENCE; DISEASE MODELS, ANIMAL; DNA PRIMERS; GENE THERAPY; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; IMMUNOHISTOCHEMISTRY; MALE; MICE; MICE, INBRED C57BL; RECEPTORS, LDL;

EID: 78149421771     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0013424     Document Type: Article

References (50)

1. Rader DJ, Cohen J, Hobbs HH (2003) Monogenic hypercholesterolemia: New insights in pathogenesis and treatment. Journal of Clinical Investigation 111: 1795-1803.
2. Deckelbaum RJ, Lees RS, Small DM (1977) Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia. New England Journal of Medicine 296: 465-470.
3. Bilheimer DW, Goldstein JL, Grundy SM (1984) Liver transplantation to provide low-density-lipoprotein receptors and lower plasma cholesterol in a child with homozygous familial hypercholesterolemia. New England Journal of Medicine 311: 1658-1664.
4. Rela M, Muiesan P, Heaton ND, Corbally M, Hajj H, et al. (1995) Orthotopic liver transplantation for hepatic-based metabolic disorders. Transplant International 8: 41-44.
5. Beigel R, Beigel Y (2009) Homozygous familial hypercholesterolemia: Long term clinical course and plasma exchange therapy for two individual patients and review of the literature. Journal of Clinical Apheresis 24: 219-224.
6. Borberg H (2009) 26 Years of LDL - Apheresis: A review of experience. Transfusion and Apheresis Science 41: 49-59.
7. Thompson GR (2003) LDL apheresis. Atherosclerosis 167: 1-13.
8. Thompson GR, Maher VMG, Matthews S, Kitano Y, Neuwirth C, et al. (1995) Familial Hypercholesterolaemia Regression Study: A randomised trial of lowdensity- lipoprotein apheresis. Lancet 345: 811-816+807-808.
9. Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, et al. (1994) Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nature Genetics 6: 335-341.
10. Grossman M, Rader DJ, Muller DWM, Kolansky DM, Kozarsky I, et al. (1995) A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nature Medicine 1: 1148-1154.
11. Vaessen SFC, Twisk J, Kastelein JJP, Kuivenhoven JA (2007) Gene therapy in disorders of lipoprotein metabolism. Current Gene Therapy 7: 35-47.
12. Kozarsky KF, Jooss K, Donahee M, Strauss IiiJF, Wilson JM (1996) Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nature Genetics 13: 54-62.
13. Kozarsky KF, McKinley DR, Austin LL, Raper SE, Stratford-Perricaudet LD, et al. (1994) In vivo correction of low density lipoprotein receptor deficiency in the Watanabe heritable hyperlipidemic rabbit with recombinant adenoviruses. Journal of Biological Chemistry 269: 13695-13702.
14. Nomura S, Merched A, Nour E, Dieker C, Oka K, et al. (2004) Low-density lipoprotein receptor gene therapy using helper-dependent adenovirus produces long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia. Gene Therapy 11: 1540-1548.
15. McCaffrey AP, Fawcett P, Nakai H, McCaffrey RL, Ehrhardt A, et al. (2008) The host response to adenovirus, helper-dependent adenovirus, and adenoassociated virus in mouse liver. Molecular Therapy 16: 931-941.
16. Wu Z, Asokan A, Samulski RJ (2006) Adeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy. Molecular Therapy 14: 316-327.
17. Chen SJ, Rader DJ, Tazelaar J, Kawashiri MA, Gao GP, et al. (2000) Prolonged correction of hyperlipidemia in mice with familial hypercholesterolemia using an adeno-associated viral vector expressing very-low-density lipoprotein receptor. Molecular Therapy 2: 256-261.
18. Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, et al. (2002) Novel adenoassociated viruses from rhesus monkeys as vectors for human gene therapy. Proceedings of the National Academy of Sciences of the United States of America 99: 11854-11859.
19. Kitajima K, Marchadier DHL, Miller GC, Gao GP, Wilson JM, et al. (2006) Complete prevention of atherosclerosis in ApoE-deficient mice by hepatic human ApoE gene transfer with adeno-associated virus serotypes 7 and 8. Arteriosclerosis, Thrombosis, and Vascular Biology 26: 1852-1857.
20. Wang L, Calcedo R, Nichols TC, Bellinger DA, Dillow A, et al. (2005) Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy. Blood 105: 3079-3086.
21. Wang L, Wang H, Bell P, McCarter RJ, He J, et al. (2009) Systematic Evaluation of AAV Vectors for Liver directed Gene Transfer in Murine Models. Molecular Therapy.
22. Lebherz C, Gao G, Louboutin JP, Millar J, Rader D, et al. (2004) Gene therapy with novel adeno-associated virus vectors substantially diminishes atherosclerosis in a murine model of familial hypercholesterolemia. Journal of Gene Medicine 6: 663-672.
23. Powell-Braxton L, VÃniant M, Latvala RD, Hirano KI, Won WB, et al. (1998) A mouse model of human familial hypercholesterolemia: Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet. Nature Medicine 4: 934-938.
24. Daugherty A (2002) Mouse models of atherosclerosis. American Journal of the Medical Sciences 323: 3-10.
25. Sanan DA, Newland DL, Tao R, Marcovina S, Wang J, et al. (1998) Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: No accentuation by apolipoprotein(a). Proceedings of the National Academy of Sciences of the United States of America 95: 4544-4549.
26. Tangirala RK, PraticA ̃ 3 D, FitzGerald GA, Chun S, Tsukamoto K, et al. (2001) Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. Journal of Biological Chemistry 276: 261-266.
27. Tangirala RK, Tsukamoto K, Chun SH, Usher D, Pure ́ E, et al. (1999) Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 100: 1816-1822.
28. Ness GC, Zhao Z (1994) Thyroid hormone rapidly induces hepatic LDL receptor mRNA levels in hypophysectomized rats. Archives of Biochemistry and Biophysics 315: 199-202.
29. Tsukamoto K, Tangirala RK, Chun S, Usher D, Pure E, et al. (2000) Hepatic Expression of Apolipoprotein E Inhibits Progression of Atherosclerosis without Reducing Cholesterol Levels in LDL Receptor-Deficient Mice. Molecular Therapy 1: 189-194.
30. Schale S, Renner M, Longhurst S, Narayanan G (2009) Regulatory requirements for clinical trial and marketing authorisation application for gene therapy medicinal products. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. pp 1-8.
31. Goldstein JL, Brown MS, Anderson RG, Russell DW, Schneider WJ (1985) Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annual review of cell biology 1: 1-39.
32. Jacobs F, Wisse E, De Geest B () The Role of Liver Sinusoidal Cells in Hepatocyte-Directed Gene Transfer. Am J Pathol 176: 14-21.
33. Soutar AK, Naoumova RP (2007) Mechanisms of Disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med 4: 214-225.
34. Garg A, Misra A (2002) Hepatic Steatosis, Insulin Resistance, and Adipose Tissue Disorders. J Clin Endocrinol Metab 87: 3019-3022.
35. Russell JC, Proctor SD () Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis. Cardiovascular Pathology 15: 318-330.
36. Moghadasian MH, Frohlich JJ, McManus BM () Advances in Experimental Dyslipidemia and Atherosclerosis. Lab Invest 81: 1173-1183.
37. Scanu A, Khalil A, Neven L, Tidore M, Dawson G, et al. (1988) Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor. J Lipid Res 29: 1671-1681.
38. Wright JF (2008) Manufacturing and characterizing AAV-based vectors for use in clinical studies. Gene Therapy 15: 840-848.
39. Cichon G, Willnow T, Herwig S, Uckert W, Löser P, et al. (2004) Nonphysiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage. The Journal of Gene Medicine 6: 166-175.
40. Hibbitt OC, McNeil E, Lufino MMP, Seymour L, Channon K, et al. (2009) Long-term Physiologically Regulated Expression of the Low-density Lipoprotein Receptor In Vivo Using Genomic DNA Mini-gene Constructs. Mol Ther.
41. Wang L, Calcedo R, Wang H, Bell P, Grant R, et al. (2009) The Pleiotropic Effects of Natural AAV Infections on Liver-directed Gene Transfer in Macaques. Mol Ther 18: 126-134.
42. Gao G, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R, et al. (2004) Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues. J Virol 78: 6381-6388.
43. Calcedo R, Vandenberghe LukA and H, Gao G, Lin J, Wilson James A and M (2009) Worldwide Epidemiology of Neutralizing Antibodies to Adeno Associated Viruses. The Journal of Infectious Diseases 199: 381-390.
44. Breous E, Somanathan S, Vandenberghe LH, Wilson JM (2009) Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T cell tolerance to antigens targeting murine liver. Hepatology 50: 612-621.
45. Gao G, Wang Q, Calcedo R, Mays L, Bell P, et al. (2009) Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Human Gene Therapy 20: 930-942.
46. Sarkar R, Tetreault R, Gao G, Wang L, Bell P, et al. (2004) Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype. Blood 103: 1253-1260.
47. Manno CS, Arruda VR, Pierce GF, Glader B, Ragni M, et al. (2006) Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nature Medicine 12: 342-347.
48. Hasbrouck NC, High KA (2008) AAV-mediated gene transfer for the treatment of hemophilia B: problems and prospects. Gene Ther 15: 870-875.
49. Vandenberghe LH, Wang L, Somanathan S, Zhi Y, Figueredo J, et al. (2006) Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid. Nat Med 12: 967-971.
50. Mays LE, Vandenberghe LH, Xiao R, Bell P, Nam H-J, et al. (2009) Adeno-Associated Virus Capsid Structure Drives CD4-Dependent CD8+ T Cell Response to Vector Encoded Proteins. J Immunol 182: 6051-6060.