Genomes and Genes
M J Graham
Affiliation: Isis Pharmaceuticals
- Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humansMark J Graham
Isis Pharmaceuticals, Carlsbad, CA 92010, USA
Circ Res 112:1479-90. 2013..Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic...
- Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic miceMark J Graham
Cardiovascular Group, Department of Antisense Drug Discovery, Isis Pharmaceuticals, Inc, Carlsbad, CA 92008, USA
J Lipid Res 48:763-7. 2007..Antisense inhibition of PCSK9 is an attractive and novel therapeutic approach for treating hypercholesterolemia in human...
- Hepatic distribution of a phosphorothioate oligodeoxynucleotide within rodents following intravenous administrationM J Graham
Isis Pharmaceuticals, Inc, Carlsbad Research Center, 1896 Rutherford Rd, Carlsbad, CA 92008, USA
Biochem Pharmacol 62:297-306. 2001..Based upon these data, it would appear that subcellular oligonucleotide disposition and metabolism among rodent species are more divergent than whole organ pharmacokinetics might predict...
- In vivo distribution and metabolism of a phosphorothioate oligonucleotide within rat liver after intravenous administrationM J Graham
Isis Pharmaceuticals, Inc, Carlbad Research Center, Carlsbad, California, USA
J Pharmacol Exp Ther 286:447-58. 1998..Our results suggest that although pharmacokinetic parameters vary as a function of hepatic cell type, significant intracellular delivery can be readily achieved in the liver after systemic administration...
- Phosphorothioate oligodeoxynucleotides distribute similarly in class A scavenger receptor knockout and wild-type miceM Butler
Isis Pharmaceuticals, Carlsbad, California, USA
J Pharmacol Exp Ther 292:489-96. 2000....
- Metabolism of antisense oligonucleotides in rat liver homogenatesR M Crooke
Isis Pharmaceuticals, Inc, Carlsbad Research Center, Carlsbad, CA 92008, USA
J Pharmacol Exp Ther 292:140-9. 2000....
- Antisense properties of 2'-O-dimethylaminooxyethyl (2'-O-DMAOE) oligonucleotidesT P Prakash
Isis Pharmaceuticals, 2292 Faraday Ave, Carlsbad, California 92008, USA
Nucleosides Nucleotides Nucleic Acids 20:829-32. 2001..This modification exhibits very high nuclease resistance and efficacy in various biological (ICAM-1, C-raf and PKC-alpha) targets...
- Altered hepatic triglyceride content after partial hepatectomy without impaired liver regeneration in multiple murine genetic modelsElizabeth P Newberry
Department of Medicine, School of Medicine, Washington University, St Louis, MO 63110, USA
Hepatology 48:1097-105. 2008..However, in no model -- and over a >90-fold range of hepatic TG content -- was liver regeneration significantly impaired following PH...
- Inhibition of ADRP prevents diet-induced insulin resistanceGladys M Varela
Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd, 712A Clinical Research Bldg, Philadelphia, PA 19104, USA
Am J Physiol Gastrointest Liver Physiol 295:G621-8. 2008..These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance...
- Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic miceEsther Merki
University of California San Diego, La Jolla, CA 92093 0682, USA
Circulation 118:743-53. 2008..Lipoprotein (a) [Lp(a)] is a genetic cardiovascular risk factor that preferentially binds oxidized phospholipids (OxPL) in plasma. There is a lack of therapeutic agents that reduce plasma Lp(a) levels...
- In vivo antisense oligonucleotide reduction of NPC1 expression as a novel mouse model for Niemann Pick type C- associated liver diseaseVictoria M Rimkunas
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA
Hepatology 47:1504-12. 2008..Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis...
- Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol lossJ Mark Brown
Department of Pathology, Biochemistry, and Orthopedic Surgery, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1040, USA
J Biol Chem 283:10522-34. 2008..Collectively, these studies provide the first insight into the hepatic itinerary of cholesterol when cholesterol esterification is inhibited only in the liver, and provide evidence for a novel non-biliary route of fecal sterol loss...
- Reduction of hepatosteatosis and lipid levels by an adipose differentiation-related protein antisense oligonucleotideYumi Imai
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19010, USA
Gastroenterology 132:1947-54. 2007..We postulated that a reduction in ADRP would ameliorate hepatic steatosis and improve insulin action...
- Liver-specific inhibition of acyl-coenzyme a:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- miceThomas A Bell
Department of Pathology, Section on Lipid Sciences, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157, USA
Arterioscler Thromb Vasc Biol 26:1814-20. 2006..The purpose of this study was to determine the effects of liver-specific inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) on the development of hypercholesterolemia and atherosclerosis in mice...
- Aberrant hepatic expression of PPARgamma2 stimulates hepatic lipogenesis in a mouse model of obesity, insulin resistance, dyslipidemia, and hepatic steatosisYuan Li Zhang
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Biol Chem 281:37603-15. 2006..The mechanism whereby hepatic Ppargamma2 gene expression is increased and how PPARgamma2 stimulates lipogenesis is under investigation...
- Modification of MyD88 mRNA splicing and inhibition of IL-1beta signaling in cell culture and in mice with a 2'-O-methoxyethyl-modified oligonucleotideTimothy A Vickers
Department of Functional Genomics, Isis Pharmaceuticals, 1896 Rutherfored Road, Carlsbad, CA 92008, USA
J Immunol 176:3652-61. 2006....
- An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosisRosanne M Crooke
Cardiovascular Group, Antisense Drug Discovery, Isis Pharmaceuticals, Inc, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
J Lipid Res 46:872-84. 2005....
- Antisense oligonucleotide blockade of alpha 4 integrin prevents and reverses clinical symptoms in murine experimental autoimmune encephalomyelitisKathleen J Myers
Antisense Drug Discovery, Isis Pharmaceuticals, 2292 Faraday Ave, Carlsbad, CA 92008, USA
J Neuroimmunol 160:12-24. 2005..These results demonstrate the potential utility of systemically administered antisense oligonucleotides for the treatment of central nervous system inflammation...
- 2'-O-[2-[(N,N-dimethylamino)oxy]ethyl]-modified oligonucleotides inhibit expression of mRNA in vitro and in vivoThazha P Prakash
Isis Pharmaceuticals Inc, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
Nucleic Acids Res 32:828-33. 2004..These results demonstrate that 2'-O-DMAOE- modified oligonucleotides are useful for antisense-based therapeutics when either RNase H-dependent or RNase H-independent target reduction mechanisms are employed...
- A mouse monoclonal antibody specific for mouse apoB48 and apoB100 produced by immunizing "apoB39-only" mice with mouse apoB48Anh T Nguyen
Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada K1Y 4W7
Biochim Biophys Acta 1761:182-5. 2006..The antibody will be an important reagent for studying mouse models of atherosclerosis. The study also underscores the utility of genetically modified mice for generating mouse mAbs against mouse proteins...
- Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein BJohn J P Kastelein
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, PO Box 22700, Room F4 159 2, 1100 DE Amsterdam, The Netherlands
Circulation 114:1729-35. 2006..In the present study, we describe the outcome of the first-in-humans study on the safety and efficacy of an antisense oligonucleotide inhibitor of apoB...