Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides

Advanced Drug Delivery Reviews

Volumn 87, Issue , 2015, Pages 46-51

  Geary, Richard S ^a   Norris, Daniel ^a   Yu, Rosie ^a   Bennett, C Frank ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

Biodistribution; Cell uptake; Oligonucleotide; Pharmacokinetics

Indexed keywords

BINDING ENERGY; BIOCHEMISTRY; BONE; PHARMACOKINETICS; PLASMA STABILITY; PROTEINS; RNA; TISSUE;

ANTISENSE OLIGONUCLEOTIDES; BIODISTRIBUTIONS; BLOOD-BRAIN BARRIER; CELL UPTAKE; GLOMERULAR FILTRATION; INTRACELLULAR TRAFFICKING; PHARMACOKINETIC PROPERTIES; PLASMA PROTEIN BINDING;

OLIGONUCLEOTIDES;

2' O METHOXYETHYL ANTISENSE OLIGONUCLEOTIDE; ANTISENSE OLIGONUCLEOTIDE; MESSENGER RNA; UNCLASSIFIED DRUG; PLASMA PROTEIN; PROTEIN BINDING;

AMYOTROPHIC LATERAL SCLEROSIS; BINDING AFFINITY; CANCER THERAPY; CELL TRANSPORT; CELLULAR DISTRIBUTION; CEREBROSPINAL FLUID; CHEMICAL MODIFICATION; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG POTENCY; DRUG TARGETING; DRUG UPTAKE; ENDOCYTOSIS; ENDOSOME; HUMAN; KIDNEY; LIVER; LIVER CELL; NONHUMAN; PHARMACODYNAMICS; PHARMACOKINETICS; PRIORITY JOURNAL; REVIEW; RNA BINDING; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; ANIMAL; ANTIBODY SPECIFICITY; CHEMISTRY; DRUG DESIGN; INTRASPINAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; NEOPLASMS; SPECIES DIFFERENCE; SUBCUTANEOUS DRUG ADMINISTRATION; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD PROTEINS; DRUG DESIGN; ENDOCYTOSIS; HUMANS; INJECTIONS, INTRAVENOUS; INJECTIONS, SPINAL; INJECTIONS, SUBCUTANEOUS; NEOPLASMS; OLIGONUCLEOTIDES, ANTISENSE; ORGAN SPECIFICITY; PROTEIN BINDING; SPECIES SPECIFICITY; TISSUE DISTRIBUTION;

EID: 84937252963     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2015.01.008     Document Type: Review

References (43)

1. Crooke S.T., Vickers T., Lima W.F., Wu H. Mechanisms of antisense drug action, an introduction. Antisense Drug Technology: Principles, Strategies, and Applications 2007, 3-46. CRC Press, Boca Raton. 2nd ed. S.T. Crooke (Ed.).
2. Bennett C.F., Swayze E.E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol. 2010, 50:259-293.
3. Wu H., Lima W.F., Zhang H., Fan A., Sun H., Crooke S.T. Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J Biol Chem. 2004, 279:17181-17189.
4. Haley B., Zamore P.D. Kinetic analysis of the RNAi enzyme complex. Nat Struct Mol Biol Jul 2004, 11(7):599-606.
5. Levin A.A., Yu R.Z., Geary R.S. Basic principles of the pharmacokinetics of antisense oligonucleotide drugs. Antisense Drug Technology: Principles, Strategies, and Applications 2007, 183-216. CRC Press, Boca Raton. 2nd ed. S.T. Crooke (Ed.).
6. Geary R.S. Antisense oligonucleotide pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2009, 5:381-391.
7. Yu R.Z., Grundy J.S., Geary R.S. Clinical pharmacokinetics of second generation antisense oligonucleotides. Expert Opin Drug Metab Toxicol. 2013, 9:169-182.
8. Crooke S.T., Geary R.S. Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B. Br J Clin Pharmacol. 2013, 76:269-276.
9. Yu R.Z., Kim T.W., Hong A., Watanabe T.A., Gaus H.J., Geary R.S. Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab Dispos 2007, 35(3):460-468.
10. Amantana A., Iversen P.L. Pharmacokinetics and biodistribution of phosphorodiamidate morpholino antisense oligomers. Current Opinion in Pharmacology. 2005, 5:550-555.
11. Iverson P.L. Morpholinos. Antisense Drug Technology: Principles, Strategies, and Applications 2007, 565-582. CRC Press, Boca Raton. 2nd ed. S.T. Crooke (Ed.).
12. McMahon B.M., Mays D., Lipsky J., Stewart J.A., Fauq A., Richelson E. Pharmacokinetics and tissue distribution of a peptide nucleic acid after intravenous administration. Antisense Nucleic Acid Drug Dev Apr 2002, 12(2):65-70.
13. Thompson J.D., Kornbrust D.J., Foy J.W., Solano E.C., Schneider D.J., Feinstein E., Molitoris B.A., Erlich S. Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration. Nucleic Acid Ther Aug 2012, 22(4):255-264.
14. Yu R.Z., Lemonidis K.M., Graham M.J., Matson J.E., Crooke R.M., Tribble D.L., Wedel M.K., Levin A.A., Geary R.S. Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100. Biochem Pharmacol. 2009, 77:910-919.
15. Geary R.S., Yu R.Z., Siwkowski A., Levin A.A. Pharmacokinetic/pharmacodynamic properties of phosphorothioate 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides in animal and man. Antisense Drug Technology: Principles, Strategies, and Applications 2007, 305-326. CRC Press, Boca Raton. 2nd ed. S.T. Crooke (Ed.).
16. Zhang H., Cook J., Nickel J., Yu R., Stecker K., Myers K., Dean N.M. Reduction of liver Fas expression by an antisense oligonucleotide protects mice from fulminant hepatitis. Nat Biotechnol. 2000, 18:862-867.
17. Altmann K.H., Dean N.M., Fabbro D., Freier S.M., Geiger T., Haener R., Huesken D., Martin P., Monia B.P., Muller M., Natt F., Nicklin P., Phillips J., Pieles U., Sasmor H., Moser H. Second generation of antisense oligonucleotides: from nuclease resistance to biological efficacy in animals. Chimia 1996, 50:168-176.
18. Hung G., Xiao X., Peralta R., Bhattacharjee G., Murray S., Norris D., Guo S., Monia B.P. Characterization of target mRNA reduction through in situ RNA hybridization in multiple organ systems following systemic antisense treatment in animals. Nucleic Acid Ther Dec 2013, 23(6):369-378.
19. Waring J.F., Ciurlionis R., Clampit J.E., Morgan S., Gum R.J., Jolly R.A., Kroeger P., Frost L., Trevillyan J., Zinker B.A., Jirousek M., Ulrich R.G., Rondinone C.M. PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fat. Mol Cell Endocrinol May 30 2003, 203(1-2):155-168.
20. Rondinone C.M., Trevillyan J.M., Clampit J., Gum R.J., Berg C., Kroeger P., Frost L., Zinker B.A., Reilly R., Ulrich R., Butler M., Monia B.P., Jirousek M.R., Waring J.F. Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes Aug 2002, 51(8):2405-2411.
21. Zinker B.A., Rondinone C.M., Trevillyan J.M., Gum R.J., Clampit J.E., Waring J.F., Xie N., Wilcox D., Jacobson P., Frost L., Kroeger P.E., Reilly R.M., Koterski S., Opgenorth T.J., Ulrich R.G., Crosby S., Butler M., Murray S.F., McKay R.A., Bhanot S., Monia B.P., Jirousek M.R. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci U S A Aug 20 2002, 99(17):11357-11362.
22. Chi K.N., Siu L.L., Hirte H., Hotte S.J., Knox J., Kollmansberger C., Gleave M., Guns E., Powers J., Walsh W., Tu D., Eisenhauer E. A phase I study of OGX-011, a 2'-methoxyethyl phosphorothioate antisense to clusterin, in combination with docetaxel in patients with advanced cancer. Clin Cancer Res Feb 1 2008, 14(3):833-839.
23. Talbot D.C., Ranson M., Davies J., Lahn M., Callies S., André V., Kadam S., Burgess M., Slapak C., Olsen A.L., McHugh P.J., de Bono J.S., Matthews J., Saleem A., Price P. Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: a proof-of-concept, first-in-human dose study. Clin Cancer Res Dec 15 2010, 16(24):6150-6158.
24. MacLeod A.R. Antisense therapies for cancer: Bridging the pharmacogenomic divide. Drug Discov Today June 21 2014, (Online).
25. van Deutekom J.C., Janson A.A., Ginjaar I.B., Frankhuizen W.S., Aartsma-Rus A., Bremmer-Bout M., den Dunnen J.T., Koop K., van der Kooi A.J., Goemans N.M., de Kimpe S.J., Ekhart P.F., Venneker E.H., Platenburg G.J., Verschuuren J.J., van Ommen G.J. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med Dec 27 2007, 357(26):2677-2686.
26. Mendell J.R., Rodino-Klapac L.R., Sahenk Z., Roush K., Bird L., Lowes L.P., Alfano L., Gomez A.M., Lewis S., Kota J., Malik V., Shontz K., Walker C.M., Flanigan K.M., Corridore M., Kean J.R., Allen H.D., Shilling C., Melia K.R., Sazani P., Saoud J.B., Kaye E.M., Eteplirsen Study Group Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol Nov 2013, 74(5):637-647.
27. Wheeler T.M., Leger A.J., Pandey S.K., MacLeod A.R., Nakamori M., Cheng S.H., Wentworth B.M., Bennett C.F., Thornton C.A. Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature Aug 2 2012, 488(7409):111-115.
28. Butler M., McKay R.A., Popoff I.J., Gaarde W.A., Witchell D., Murray S.F., Dean N.M., Bhanot S., Monia B.P. Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. Diabetes Apr 2002, 51(4):1028-1034.
29. Lieberman A.P., Yu Z., Murray S., Peralta R., Low A., Guo S., Yu X.X., Cortes C.J., Bennett C.F., Monia B.P., La Spada A.R., Hung G. Peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy. Cell Rep May 8 2014, 7(3):774-784.
30. Cortes C.J., Ling S.C., Guo L.T., Hung G., Tsunemi T., Ly L., Tokunaga S., Lopez E., Sopher B.L., Bennett C.F., Shelton G.D., Cleveland D.W., La Spada A.R. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy. Neuron Apr 16 2014, 82(2):295-307.
31. Smith R.A., Miller T.M., Yamanaka K., Monia B.P., Condon T.P., Hung G., Lobsiger C.S., Ward C.M., McAlonis-Downes M., Wei H., Wancewicz E.V., Bennett C.F., Cleveland D.W. Antisense oligonucleotide therapy for neurodegenerative disease. J Clin Invest Aug 2006, 116(8):2290-2296.
32. Kordasiewicz H.B., Stanek L.M., Wancewicz E.V., Mazur C., McAlonis M.M., Pytel K.A., Artates J.W., Weiss A., Cheng S.H., Shihabuddin L.S., Hung G., Bennett C.F., Cleveland D.W. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron Jun 21 2012, 74(6):1031-1044.
33. Passini M.A., Bu J., Richards A.M., Kinnecom C., Sardi S.P., Stanek L.M., Hua Y., Rigo F., Matson J., Hung G., Kaye E.M., Shihabuddin L.S., Krainer A.R., Bennett C.F., Cheng S.H. Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci Transl Med. Mar 2 2011, 3(72):72ra18.
34. Rigo F., Chun S.J., Norris D.A., Hung G., Lee S., Matson J., Fey R.A., Gaus H., Hua Y., Grundy J.S., Krainer A.R., Henry S.P., Bennett C.F. Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates. J Pharmacol Exp Ther Jul 2014, 350(1):46-55.
35. Miller T.M., Pestronk A., David W., Rothstein J., Simpson E., Appel S.H., Andres P.L., Mahoney K., Allred P., Alexander K., Ostrow L.W., Schoenfeld D., Macklin E.A., Norris D.A., Manousakis G., Crisp M., Smith R., Bennett C.F., Bishop K.M., Cudkowicz M.E. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol May 2013, 12(5):435-442.
36. Rigo F., Chun S.J., Norris D.A., Hung G., Lee S., Matson J., Fey R.A., Gaus H., Hua Y., Grundy J.S., Krainer A.R., Henry S.P., Bennett C.F. Adult and Juvenile Monkey Pharmacokinetics (PK) of a Uniformly Modi_ed 2'-(2-Methoxyethyl) Antisense Oligonucleotide(ASO; ISIS-SMNRx) in Development for Treatment of Spinal Muscular Atrophy (SMA). Poster Presentation, 2012 AAPS Annual Meeting and Exposition, Chicago, IL, October 14-18 2012.
37. Norris D.A., Shabir R., John B., Mazur C., Beconi M., Bennett F., Grundy J.S. Pharmacokinetics (PK) of an 35S-labeled Second Generation Antisense Oligonucleotide (ASO) in Mice and Rats After Intracerebroventricular (ICV) and/or Intrathecal (IT) Single Dose Administration. Poster Presentation, 2013 AAPS Annual Meeting and Exposition, San Antonio, TX, Nov 10-14 2013.
38. Ostergaard M.E., Southwell A.L., Kordasiewicz H., Watt A.T., Skotte N.H., Doty C.N., Vaid K., Villanueva E.B., Swayze E.E., Bennett C.F., Hayden M.R., Seth P.P. Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res Nov 2013, 41(21):9634-9650.
39. Geary R.S., Wancewicz E., Matson J., Pearce M., Siwkowski A., Swayze E., Bennett C.F. Effect of dose and plasma concentration on liver uptake and pharmacologic activity of a 2'-methoxyethyl modified chimeric antisense oligonucleotide targeting PTEN. Biochem Pharmacol Aug 1 2009, 78(3):284-291.
40. Liang X.H., Shen W., Sun H., Prakash T.P., Crooke S.T. TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells. Nucleic Acids Res 2014, 42(12):7819-7832.
41. Koller E., Vincent T.M., Chappell A., De S., Manoharan M., Bennett C.F. Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes. Nucleic Acids Res Jun 2011, 39(11):4795-4807.
42. Kanasty R., Dorkin J.R., Vegas A., Anderson D. Delivery materials for siRNA therapeutics. Nat Mater Nov 2013, 12(11):967-977.
43. Prakash T.P., Graham M.J., Yu J., Carty R., Low A., Chappell A., Schmidt K., Zhao C., Aghajan M., Murray H.F., Riney S., Booten S.L., Murray S.F., Gaus H., Crosby J., Lima W.F., Guo S., Monia B.P., Swayze E.E., Seth P.P. Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice. Nucleic Acids Res 2014, 42(13):8796-8807.