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Reviews

Gene therapy for dyslipidemia: a review of gene replacement and gene inhibition strategies

Sadik H KassimDepartment of Pathology & Laboratory Medicine1University of Pennsylvania School of Medicine, Gene Therapy Program, 125 South 31st Street (Suite 2000), PA 19104, USA
,
James M WilsonDepartment of Pathology & Laboratory Medicine, University of Pennsylvania School of
&
Daniel J RaderInstitute for Translational Medicine & Therapeutics1University of Pennsylvania School of Medicine, Room 654, Biomedical Research Building II/III, PA 19104-16160, 421 Curie Boulevard, USA
Pages 793-809 | Published online: 18 Jan 2017

  • Hegele RA: Plasma lipoproteins, genetic influences and clinical implications. Nat. Rev. Genet. 10, 109–121 (2009).
  • Lloyd-Jones D, Adams RJ, Brown TM et al.: Executive summary, Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation 121, E46–E215 (2010).
  • Dietz HC: Genomic medicine: new therapeutic approaches to mendelian disorders. N. Engl. J. Med. 363, 852–863 (2010).
  • Nguyen TH, Ferry N: Liver gene therapy: advances and hurdles. Gene Ther. 11, S76–S84 (2004).
  • Ross CJD, Twisk J, Meulenberg JM et al.: Long-term correction of murine lipoprotein lipase deficiency with AAV1-mediated gene transfer of the naturally occurring LPLS447X beneficial mutation. Hum. Gene Ther. 15, 906–919 (2004).
  • Athanasopulos T, Owen JS, Hassall DG et al.: Intramuscular injection of a plasmid vector expressing human apolipoprotein E limits progression of xanthoma and aortic atheroma in apoE-deficient mice. Hum. Mol. Genet. 9, 2545–2551 (2000).
  • Shyh-Dar L, Song L, Leaf H: Lipoplex and LPD nanoparticles for in vivo gene delivery. Cold Spring Harb. Protoc. DOI:10.1101/pdb. prot4448 (2006) (Epub ahead of print).
  • Li SD, Huang L: Gene therapy progress and prospects: nonviral gene therapy by systemic delivery. Gene Ther. 13, 1313–1319 (2006).
  • Budker V, Zhang G, Knechtle S, Wolff JA: Naked DNA delivered intraportally expresses efficiently in hepatocytes. Gene Ther. 3, 593–598 (1996).
  • Thomas CE, Ehrhardt A, Kay MA: Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4, 346–358 (2003).
  • Jooss K, Ertl HCJ, Wilson JM: Cytotoxic T-lymphocyte target proteins and their major histocompatibility complex class I restriction in response to adenovirus vectors delivered to mouse liver. J. Virol. 72, 2945–2954 (1998).
  • Kay MA, Meuse L, Gown AM et al.: Transient immunomodulation with anti-CD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirus-mediated gene transfer into mouse liver. Proc. Natl Acad. Sci. USA 94, 4686–4691 (1997).
  • Yang Y, Su Q, Grewal IS et al.: Transient subversion of CD40 ligand function diminishes immune responses to adenovirus vectors in mouse liver and lung tissues. J. Virol. 70, 6370–6377 (1996).
  • Seiler MP, Cerullo V, Lee B: Immune response to helper dependent adenoviral mediated liver gene therapy: challenges and prospects. Curr. Gene Ther. 7, 297–305 (2007).
  • Flotte TR: New AAV serotypes may broaden the therapeutic pipeline to human gene therapy. Mol. Ther. 13, 1–2 (2006).
  • Gao G, Vandenberghe LH, Wilson JM: New recombinant serotypes of AAV vectors. Curr. Gene Ther. 5, 285–297 (2005).
  • Gao G, Alvira MR, Somanathan S et al.: Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc. Natl Acad. Sci. USA 100, 6081–6086 (2003).
  • Wang L, Wang H, Bell P et al.: Systematic evaluation of AAV vectors for liver directed gene transfer in murine models. Mol. Ther. 18, 118–125 (2010).
  • Wang L, Calcedo R, Wang H et al.: The pleiotropic effects of natural AAV infections on liver-directed gene transfer in macaques. Mol. Ther. 18, 126–134 (2010).
  • Gao G, Vandenberghe LH, Alvira MR et al.: Clades of adeno-associated viruses are widely disseminated in human tissues. J. Virol. 78, 6381–6388 (2004).
  • Chao HJ, Liu YB, Rabinowitz J et al.: Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Mol. Ther. 2, 619–623 (2000).
  • Blankinship MJ, Gregorevic P, Allen JM et al.: Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Mol. Ther. 10, 671–678 (2004).
  • McCarty DM: Self-complementary AAV vectors: advances and applications. Mol. Ther. 16, 1648–1656 (2008).
  • Crooke ST: Progress in antisense technology. Ann. Rev. Med. 61–95 (2004).
  • Lee SH, Sinko PJ: SiRNA – getting the message out. Eur. J. Pharm. Sci. 27, 401–410 (2006).
  • Sontheimer EJ: Assembly and function of RNA silencing complexes. Nat. Rev. Mol. Cell Biol. 6, 127–138 (2005).
  • Haasnoot J, Berkhout B: Nucleic acids-based therapeutics in the battle against pathogenic viruses. Handb. Exp. Pharmacol. (189), 243–263 (2009).
  • Grimm D, Streetz KL, Jopling CL et al.: Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537–541 (2006).
  • Giering JC, Grimm D, Storm TA, Kay MA: Expression of shRNA from a tissue-specific pol II promoter is an effective and safe RNAi therapeutic. Mol. Ther. 16, 1630–1636 (2008).
  • Ginsburg GS: Regression of atherosclerosis with therapeutic antibodies: pipe cleaner or pipe dream? J. Am. Coll. Cardiol. 50, 2319–2321 (2007).
  • Rader DJ, Cohen J, Hobbs HH: Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J. Clin. Invest. 111, 1795–1803 (2003).
  • Moorjani S, Roy M, Gagne C et al.: Homozygous familial hypercholesterolemia among French Canadians in Quebec province. Arteriosclerosis 9, 211–216 (1989).
  • Khachadu Ak, Uthman SM: Experiences with homozygous cases of familial hypercholesterolemia. A report of 52 patients. Nutrition Metab. 15, 132–140 (1973).
  • Seftel HC, Baker SG, Sandler MP et al.: A host of hypercholesterolemic homozygotes in South Africa. BMJ 281, 633–636 (1980).
  • Goldstein JL, Brown MS: The LDL receptor defect in familial hypercholesterolemia: implications for pathogenesis and therapy. Med. Clin. N. Am. 66, 335–362 (1982).
  • Kolansky DM, Cuchel M, Clark BJ et al.: Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am. J. Cardiol. 102, 1438–1443 (2008).
  • Moghadasian MH, Frohlich JJ, Saleem M et al.: Surgical management of dyslipidemia: clinical and experimental evidence. J. Invest. Surg. 14, 71–78 (2001).
  • Lopez-Santamaria M, Migliazza L, Gamez M et al.: Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal pass. J. Pediatr. Surg. 35, 630–633 (2000).
  • Thompsen J, Thompson PD: A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis 189, 31–38 (2006).
  • Sachais BS, Katz J, Ross J, Rader DJ: Long-term effects of LDL apheresis in patients with severe hypercholesterolemia. J. Clin. Apher. 20, 252–255 (2005).
  • Grossman M, Rader DJ, Muller DWM et al.: A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat. Med. 1, 1148–1154 (1995).
  • Grossman M, Raper SE, Kozarsky K et al.: Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat. Genet. 6, 335–341 (1994).
  • Daugherty A: Mouse models of atherosclerosis. Am. J. Med. Sci. 323, 3–10 (2002).
  • Rader DJ, Tietge UJ: Gene therapy for dyslipidemia: clinical prospects. Curr. Atheroscler. Rep. 1, 58–69 (1999).
  • Zhang SH, Reddick RL, Piedrahita JA, Maeda N: Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258, 468–471 (1992).
  • Kozarsky KF, Jooss K, Donahee M, Strauss III JF, Wilson JM: Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nat. Genet.13, 54–62 (1996).
  • Kozarsky KF, McKinley DR, Austin LL et al.: In vivo correction of low density lipoprotein receptor deficiency in the Watanabe heritable hyperlipidemic rabbit with recombinant adenoviruses. J. Biol. Chem. 269, 13695–13702 (1994).
  • Chen SJ, Rader DJ, Tazelaar J et al.: Prolonged correction of hyperlipidemia in mice with familial hypercholesterolemia using an adeno-associated viral vector expressing very-low-density lipoprotein receptor. Mol. Ther. 2, 256–261 (2000).
  • Lebherz C, Gao G, Louboutin JP et al.: Gene therapy with novel adeno-associated virus vectors substantially diminishes atherosclerosis in a murine model of familial hypercholesterolemia. J. Gene Med. 6, 663–672 (2004).
  • Kankkonen HM, Vähäkangas E, Marr RA et al.: Long-term lowering of plasma cholesterol levels in LDL-receptor-deficient WHHL rabbits by gene therapy. Mol. Ther. 9, 548–556 (2004).
  • Nomura S, Merched A, Nour E et al.: Low-density lipoprotein receptor gene therapy using helper-dependent adenovirus produces long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia. Gene Ther. 11, 1540–1548 (2004).
  • Williams KJ, Feig JE, Fisher EA: Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat. Clin. Pract. Cardiovasc. Med. 5, 91–102 (2008).
  • Sadik H, Kassim HL, Luk H et al.: Rader gene therapy in a humanized mouse model of familial hypercholesterolemia leads to marked regression of atherosclerosis. PLoS One 5(10), E13424 (2010).
  • Hibbitt OC, Harbottle RP, Waddington SN et al.: Delivery and long-term expression of a 135 kb LDLR genomic DNA locus in vivo by hydrodynamic tail vein injection. J. Gene Med. 9, 488–497 (2007).
  • Hibbitt OC, McNeil E, Lufino MMP et al.: Long-term physiologically regulated expression of the low-density lipoprotein receptor in vivo using genomic DNA mini-gene constructs. Mol. Ther. 18, 317–326 (2010).
  • Crooke RM: Antisense oligonucleotides as therapeutics for hyperlipidaemias. Exp. Opin. Biol. Ther. 5, 907–917 (2005).
  • Crooke RM, Graham MJ, Lemonidis KM et al.: An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J. Lipid Res. 46, 872–884 (2005).
  • Raal FJ, Santos RD, Blom DJ et al.: Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia, a randomised, double-blind, placebocontrolled trial. Lancet 375, 998–1006 (2010).
  • Visser ME, Akdim F, Tribble DL et al.: Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J. Lipid Res. 51, 1057–1062 (2010).
  • Visser ME, Kastelein JJP, Stroes ESG: Apolipoprotein B synthesis inhibition: results from clinical trials. Curr. Opin. Lipidol. (2010).
  • Akdim F, Visser ME, Tribble DL et al.: Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am. J. Cardiol. 105, 1413–1419 (2010).
  • Akdim F, Stroes ES, Sijbrands EJ et al.: Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J. Am. Coll. Cardiol. 55(15), 1611–1618 (2010).
  • Soutschek J, Akinc A, Bramlage B et al.: Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173–178 (2004).
  • Zimmermann TS, Lee ACH, Akinc A et al.: RNAi-mediated gene silencing in nonhuman primates. Nature 441, 111–114 (2006).
  • MacLachlan I: A Phase I study to evaluate the safety, tolerability, and pharmacokinetics of lipid nanoparticle ApoB siRNA (ApoB-SNALP) in hypercholesterolemic subjects. Presented at: American Society of Gene & Cell Therapy 13th Annual Conference. Washington, DC, USA, 17–22 May 2010.
  • Kotowski IK, Pertsemlidis A, Luke A et al.: A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am. J. Hum. Genet. 78, 410–422 (2006).
  • Abifadel M, Varret M, Rabès JP et al.: Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34, 154–156 (2003).
  • Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH: Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN et al.: Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl Acad. Sci. USA 105, 11915–11920 (2008).
  • Rader DJ: Molecular regulation of HDL metabolism and function: implications for novel therapies. J. Clin. Invest. 116, 3090–3100 (2006).
  • Alwaili K, Awan Z, Alshahrani A, Genest J: High-density lipoproteins and cardiovascular disease: 2010 update. Expert Rev. Cardiovasc. Ther. 8, 413–423 (2010).
  • Sviridov D, Nestel PJ: Genetic factors affecting HDL levels, structure, metabolism and function. Curr. Opin. Lipidol. 18, 157–163 (2007).
  • Moore RE, Kawashiri MA, Kitajima K et al.: Apolipoprotein A-I deficiency results in markedly increased atherosclerosis in mice lacking the LDL receptor. Arterioscler. Thromb. Vasc. Biol. 23, 1914–1920 (2003).
  • Moore RE, Navab M, Millar JS et al.: Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circulation Res. 97, 763–771 (2005).
  • Kopfler WP, Willard M, Betz T et al.: Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol. Circulation 90, 1319–1327 (1994).
  • De Geest B, Zhao Z, Collen D, Holvoet P: Effects of adenovirus-mediated human apoA-I gene transfer on neointima formation after endothelial denudation in apoE-deficient mice. Circulation 96, 4349–4356 (1997).
  • Tsukamoto K, Hiester KG, Smith P et al.: Comparison of human apoA-I expression in mouse models of atherosclerosis after gene transfer using a second generation adenovirus. J. Lipid Res. 38, 1869–1876 (1997).
  • Benoit P, Emmanuel F, Caillaud JM et al.: Somatic gene transfer of human apoA-I inhibits atherosclerosis progression in mouse models. Circulation 99, 105–110 (1999).
  • Tangirala RK, Tsukamoto K, Chun SH et al.: Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 100, 1816–1822 (1999).
  • De Geest B, Van Linthout S, Lox M, Collen D, Holvoet P: Sustained expression of human apolipoprotein A-I after adenoviral gene transfer in C57BL/6 mice, Role of apolipoprotein A-I promoter, apolipoprotein A-I introns, and human apolipoprotein E enhancer. Hum. Gene Ther. 11, 101–112 (2000).
  • Belalcazar LM, Merched A, Carr B et al.: Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia. Circulation 107, 2726–2732 (2003).
  • Pastore L, Belalcazar LM, Oka K et al.: Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice. Gene 327, 153–160 (2004).
  • Sharifi BG, Wu K, Wang L et al.: AAV serotypedependent apolipoprotein A-IMilano gene expression. Atherosclerosis 181, 261–269 (2005).
  • Kitajima K, Marchadier DHL, Burstein H, Rader DJ: Persistent liver expression of murine apoA-l using vectors based on adeno-associated viral vectors serotypes 5 and 1. Atherosclerosis 186, 65–73 (2006).
  • Vaessen SFC, Veldman RJ, Cornijn EM et al.: AAV gene therapy as a means to increase apolipoprotein (Apo) A-I and high-density lipoprotein-cholesterol levels: correction of murine ApoA-I deficiency. J. Gene Med. 11, 697–707 (2009).
  • Cimmino G, Chen W, Speidl WS et al.: Safe and sustained overexpression of functional apolipoprotein-AI/high-density lipoprotein in apolipoprotein-AI-null mice by muscular adeno-associated viral serotype 8 vector gene transfer. J. Cardiovasc. Pharmacol. 54, 405–411 (2009).
  • Weisgraber KH, Bersot TP, Mahley RW: A-I(Milano) apoprotein. Isolation and characterization of a cysteine-containing variant of the A-I apoprotein from human high density lipoproteins. J. Clin. Invest. 66, 901–907 (1980).
  • Gualandri V, Franceschini G, Sirtori CR: AI(Milano) apoprotein identification of the complete kindred and evidence of a dominant genetic transmission. Am. J. Hum. Genet. 37, 1083–1097 (1985).
  • Chiesa G, Sirtori CR: Recombinant apolipoprotein A-IMilano: a novel agent for the induction of regression of atherosclerotic plaques. Ann. Med. 35, 267–273 (2003).
  • Lebherz C, Sanmiguel J, Wilson JM, Rader DJ: Gene transfer of wild-type apoA-I and apoA-I Milano reduce atherosclerosis to a similar extent. Cardiovasc. Diabetol. 6, 15 (2007).
  • Alexander ET, Weibel GL, Joshi MR et al.: Macrophage reverse cholesterol transport in mice expressing ApoA-I milano. Arterioscler. Thromb. Vasc. Biol. 29, 1496–1501 (2009).
  • Santamarina-Fojo S, Peterson K, Knapper C et al.: Complete genomic sequence of the human ABCA1 gene. Analysis of the human and mouse ATP-binding cassette A promoter. Proc. Natl Acad. Sci. USA 97, 7987–7992 (2000).
  • Iatan I, Alrasadi K, Ruel I, Alwaili K, Genest J: Effect of ABCA1 mutations on risk for myocardial infarction. Curr. Atheroscler. Rep. 10, 413–426 (2008).
  • Schaefer EJ, Zech LA, Schwartz DE, Brewer HB: Coronary heart-disease prevalence and other clinical-features in familial high-density lipoprotein deficiency (tangier disease). Ann. Intern. Med. 93, 261–266 (1980).
  • Tall AR, Wang N: Tangier disease as a test of the reverse cholesterol transport hypothesis. J. Clin. Invest. 106, 1205–1207 (2000).
  • Wang X, Collins HL, Ranalletta M et al.: Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J. Clin. Invest. 117, 2216–2224 (2007).
  • Aiello RJ, Brees D, Bourassa PA et al.: Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler. Thromb. Vasc. Biol. 22, 630–637 (2002).
  • Wellington CL, Brunham LR, Zhou S et al.: Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1. J. Lipid Res. 44, 1470–1480 (2003).
  • Feng Y, Lievens J, Jacobs F et al.: Hepatocytespecific ABCA1 transfer increases HDL cholesterol but impairs HDL function and accelerates atherosclerosis. Cardiovasc. Res. 88(2), 376–385 (2010).
  • Joyce CW, Wagner EM, Basso F et al.: ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of pro-atherogenic lipoproteins and enhanced atherosclerosis. J. Biol. Chem. 281, 33053–33065 (2006).
  • Rousset X, Vaisman B, Amar M, Sethi AA, Remaley AT: Lecithin: cholesterol acyltransferase – from biochemistry to role in cardiovascular disease. Curr. Opin. Endocrinol. Diabetes Obes. 16, 163–171 (2009).
  • Sakai N, Vaisman BL, Koch CA et al.: Targeted disruption of the mouse lecithin: cholesterol acyltransferase (LCAT) gene: generation of a new animal model for human LCAT deficiency. J. Biol. Chem. 272, 7506–7510 (1997).
  • Broedl UC, Rader DJ: Gene therapy for lipoprotein disorders. Exp. Opin. Biol. Ther. 5, 1029–1038 (2005).
  • Séguret-Macé S, Latta-Mahieu M, Castro G et al.: Potential gene therapy for lecithincholesterol acyltransferase (LCAT)-deficient and hypoalphalipoproteinemic patients with adenovirus-mediated transfer of human LCAT gene. Circulation 94, 2177–2184 (1996).
  • Mertens A, Verhamme P, Bielicki JK et al.: Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice, LCAT gene transfer decreases atherosclerosis. Circulation 107, 1640–1646 (2003).
  • Van Craeyveld E, Lievens J, Jacobs F et al.: Apolipoprotein A-I and lecithin, Cholesterol acyltransferase transfer induce cholesterol unloading in complex atherosclerotic lesions. Gene Ther. 16, 757–765 (2009).
  • Rader DJ, Daugherty A: Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913 (2008).
  • Barter PJ, Caulfield M, Eriksson M et al.: Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357, 2109–2122 (2007).
  • Bhatt KN, Wells BJ, Sperling LS, Baer JT: High-density lipoprotein therapy: is there hope? Curr. Treat. Options Cardiovasc. Med. 1–14 (2010).
  • 110 Tanaka H, Ishida T, Johnston TP et al.: Role of endothelial lipase in plasma HDL levels in a murine model of hypertriglyceridemia. J. Atheroscler. Thromb. 16, 327–338 (2009).
  • Jin W, Millar JS, Broedl U, Glick JM, Rader DJ: Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. J. Clin. Invest. 111, 357–362 (2003).
  • Ishida T, Choi S, Kundu RK et al.: Endothelial lipase is a major determinant of HDL level. J. Clin. Invest. 111, 347–355 (2003).
  • Edmondson AC, Brown RJ, Kathiresan S et al.: Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J. Clin. Invest. 119, 1042–1050 (2009).
  • Garg A, Simha V: Update: update on dyslipidemia. J. Clin. Endocrinol. Metab. 92, 1581–1589 (2007).
  • Beigneux AP, Davies BSJ, Gin P et al.: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metab. 5, 279–291 (2007).
  • Peterfy M, Ben-Zeev O, Mao HZ et al.: Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia. Nat. Genet. 39, 1483–1487 (2007).
  • Rahalkar AR, Giffen F, Har B et al.: Novel LPL mutations associated with lipoprotein lipase deficiency: two case reports and a literature review. Can. J. Physiol. Pharmacol. 87, 151–160 (2009).
  • Banks PA: Practice guidelines in acute pancreatitis. Am. J. Gastroenterol. 92, 377–386 (1997).
  • Ashbourne Excoffon KJD, Liu G, Miao L et al.: Correction of hypertriglyceridemia and impaired fat tolerance in lipoprotein lipase-deficient mice by adenovirus-mediated expression of human lipoprotein lipase. Arterioscler. Thromb. Vasc. Biol. 17, 2532–2539 (1997).
  • Liu G, Ashbourne Excoffon KJD, Wilson JE et al.: Phenotypic correction of feline lipoprotein lipase deficiency by adenoviral gene transfer. Hum. Gene Ther. 11, 21–32 (2000).
  • Groenemeijer BE, Hallman MD, Reymer PW et al.: Genetic variant showing a positive interaction with b-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group. Circulation 95(12), 2628–2635. (1997).
  • Gagné SE, Larson MG, Pimstone SN et al.: A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study. Clin. Genet. 55(6), 450–454 (1999).
  • Wittrup HH, Tybjaerg-Hansen A, Steffensen R et al.: Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men, The Copenhagen city heart study. Arterioscler. Thromb. Vasc. Biol. 19, 1535–1540 (1999). Boss CJD, Twisk J, Bakker AC et al.: Correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation. Hum. Gene Ther. 17, 487–499 (2006).
  • 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 114, 2077–2086 (2009).
  • Pennacchio LA, Olivier M, Hubacek JA et al.: An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294, 169–173 (2001).
  • Tai ES, Ordovas JM: Clinical significance of apolipoprotein A5. Curr. Opin. Lipidol. 19, 349–354 (2008).
  • Van der Vliet HN, Schaap FG, Levels JHM et al.: Adenoviral overexpression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice. Biochem. Biophys. Res. Comm. 295, 1156–1159 (2002).
  • Huang W, Bi N, Zhang X et al.: Overexpression of apolipoprotein AV in the liver reduces plasma triglyceride and cholesterol but not HDL in ApoE deficient mice. Biochem. Biophys. Res. Comm. 346, 14–18 (2006).
  • Hofker MH: APOC3 null mutation affects lipoprotein profile APOC3 deficiency, from mice to man. Eur. J. Hum. Genet. 18, 1–2 (2010).
  • Smith SJ, Cases S, Jensen DR et al.: Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat. Genet. 25, 87–90 (2000).
  • Yu XX, Murray SF, Pandey SK et al.: Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice. Hepatology 42, 362–371 (2005).
  • Liu Y, Millar JS, Cromley DA et al.: Knockdown of Acyl-CoA: diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice. Biochim. Biophys. Acta 1781, 97–104 (2008).
  • Ishibashi S, Brown MS, Goldstein JL et al.: Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92, 883–893 (1993).
  • Williams KJ, Fless GM, Petrie KA et al.: Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans. J. Biol. Chem. 267, 13284–13292 (1992).
  • Signori E, Rinaldi M, Fioretti D et al.: ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice. Biochem. Biophys. Res. Comm. 361, 543–548 (2007).
  • Evans V, Foster H, Graham IR et al.: Human apolipoprotein E expression from mouse skeletal muscle by electrotransfer of nonviral DNA (plasmid) and pseudotyped recombinant adeno-associated virus (AAV2/7). Hum. Gene Ther. 19, 569–578 (2008).
  • Stevenson SC, Marshall-Neff J, Teng B et al.: Phenotypic correction of hypercholesterolemia in ApoE-deficient mice by adenovirus-mediated in vivo gene transfer. Arterioscler. Thromb. Vasc. Biol. 15, 479–484 (1995).
  • Kashyap VS, Santamarina-Fojo S, Brown DR et al.: Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors. J. Clin. Invest. 96, 1612–1620 (1995).
  • Tsukamoto K, Smith P, Glick JM, Rader DJ: Liver-directed gene transfer and prolonged expression of three major human apoE isoforms in apoE-deficient mice. J. Clin. Invest. 100, 107–114 (1997).
  • Kim IH, Jozkowicz A, Piedra PA, Oka K, Chan L: Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector. Proc. Natl Acad. Sci. USA 98, 13282–13287 (2001).
  • Tangirala RK, Pratico D, FitzGerald GA et al.: Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J. Biol. Chem. 276, 261–266 (2001).
  • Zamel R, Khan R, Pollex RL, Hegele RA: Abetalipoproteinemia: two case reports and literature review. Orphanet J. Rare Dis. 3, 19 (2008).
  • Sharp D, Blinderman L, Combs KA et al.: Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature 365, 65–69 (1993).
  • Stroes ES, Nierman MC, Meulenberg JJ et al.: Intramuscular administration of AAV1-lipoprotein lipaseS447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler. Thromb. Vasc. Biol. 28, 2303–2304 (2008).

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