RNA modulation, repair and remodeling by splice switching oligonucleotides

• Autorzy: Kole R. , Williams T. , Cohen L.
• Języki publikacji: EN

Abstrakty

EN

Targeting splicing by antisense oligonucleotides allows RNA modifications that are not possible with RNA interference or other antisense techniques that destine the RNA for destruction. By changing the ratio of naturally occurring splice variants the expression of mRNA is modulated. By preventing the use of an aberrant splice site created by a mutation and enforcing re-selection of correct splice sites the RNA is repaired. Antisense induced skipping of the exon that carries a nonsense mutation remodels the mRNA and restores the reading frame of the defective protein. All of the above approaches have clinical applications. Modulation of splice variants is par­ticularly important since close to 60% of all genes code for alternatively spliced pre-mRNA.

Słowa kluczowe

EN

antisense oligonucleotide; RNA splicing; mRNA; genetic disease

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2004
• Tom: 51
• Numer: 2
• Opis fizyczny: p.373-378,ref.

Twórcy

autor

Kole R.

• University of North Carolina, Chapel Hill, NC, 27599, USA

autor

Williams T.

autor

Cohen L.

Bibliografia

• Agami R. (2002) RNAi and related mechanisms and their potential use for therapy. Curr Opin Chem Biol.; 6: 829-34.
• Agrawal S, Temsamani J, Galbraith W, Tang J. (1995) Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet.; 28: 7-16.
• Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB. (1993) bcl- x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell.; 74: 597-608.
• Cheng TC, Orkin SH, Antonarakis SE, Potter MJ, Sexton JP, Markham AF, Giardina PJ, Li A, Kazazian HH Jr. (1984) beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc Natl Acad Sci USA.; 81: 2821-5.
• Cory S, Adams JM. (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer.; 2: 647-56.
• Crooke S. (2001) Basic principles of antisense technology. In Antisense drug technology: principles, strategies and applications. pp 1-28. Marcel Dekker, New York, NY.
• Dominski Z, Kole R. (1993) Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc Natl Acad Sci USA.; 90: 8673-7.
• Gebski BL, Mann CJ, Fletcher S, Wilton SD. (2003) Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdxmouse muscle. Hum Mol Genet.; 12: 1801-11.
• Kang SH, Cho MJ, Kole R. (1998) Up-regulation of luciferase gene expression with antisense oligonucleotides: implications and applications in functional assay development. Biochemistry.; 37: 6235-9.
• Kole R, Dominski Z. (1997) Antisense oligonucleotides which combat aberrant splicing and methods of using the same. US Patent 5,627,274.
• Lacerra G, Sierakowska H, Carestia C, Fucharoen S, Summerton J, Weller D, Kole R. (2000) Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients. Proc Natl Acad Sci USA. ; 97: 9591-6.
• Liu R, Page C, Beidler DR, Wicha MS, Nunez G. (1999) Overexpression of Bcl-x(L) promotes chemotherapy resistance of mammary tumors in a syngeneic mouse model. Am J Pathol.; 155: 1861-7.
• Lu QL, Mann CJ, Lou F, Bou-Gharios G, Morris GE, Xue SA, Fletcher S, Partridge TA, Wilton SD. (2003) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med. ; 9: 1009-14.
• Mann CJ, Honeyman K, Cheng AJ, Ly T, Lloyd F, Fletcher S, Morgan JE, Partridge TA, Wilton SD. (2001) Antisense- induced exon skipping and synthesis of dystrophin in the mdx mouse. Proc Natl Acad Sci USA. ; 98: 42-7.
• Matsuo M. (1996) Duchenne/Becker muscular dystrophy: from molecular diagnosis to gene therapy. Brain Dev.; 18: 167-72.
• Mercatante D, Kole R. (2000) Modification of alternative splicing pathways as a potential approach to chemotherapy. Pharmacol Ther.; 85: 237-43.
• Mercatante DR, Möhler JL, Kole R. (2002) Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem.; 277: 49374-82.
• Mercatante DR, Bortner CD, Cidlowski JA, Kole R. (2001) Modification of alternative splicing of Bcl-x pre-mRNA in prostate and breast cancer cells. Analysis of apoptosis and cell death. J Biol Chem.; 276: 16411-7.
• Minn AJ, Boise LH, Thompson CB. (1996) Bcl-x(S) antagonizes the protective effects of Bcl-x(L). J Biol Chem.; 271: 6306-12.
• Modrek B, Lee C. (2002) A genomic view of alternative splicing. Nat Genet.; 30: 13-9.
• Moulton HM, Hase MC, Smith KM, Iversen PL. (2003) HIV Tat peptide enhances cellular delivery of antisense morpholino oligomers. Antisense Nucleic Acid Drug Dev.; 13: 31-43.
• Olivieri NF. (1999) The beta-thalassemias. N Engl J Med.; 341: 99-109.
• Sazani P, Kang SH, Maier MA, Wei C, Dillman J, Summerton J, Manoharan M, Kole R. (2001) Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs. Nucleic Acids Res.; 29: 3965-74.
• Sazani P, Vacek MM, Kole R. (2002a) Short-term and long-term modulation of gene expression by antisense therapeutics. Curr Opin Biotechnol.; 13: 468-72.
• Sazani P, Gemignani F, Kang SH, Maier MA, Manoharan M, Persmark M, Bortner D, Kole R. (2002b) Systemically delivered antisense oligomers upregulate gene expression in mouse tissues. Nat Biotechnol.; 20: 1228-33.
• Sazani P, Astriab-Fischer A, Kole R. (2003) Effects of base modifications on antisense properties of 2'-O-methoxyethyl and PNA oligonucleotides. Antisense Nucleic Acid Drug Dev.; 13: 119-28.
• Suwanmanee T, Sierakowska H, Fucharoen S, Kole R. (2002a) Repair of a splicing defect in erythroid cells from patients with beta-thalassemia/HbE disorder. Mol Ther.; 6: 718-26.
• Suwanmanee T, Sierakowska H, Lacerra G, Svasti S, Kirby S, Walsh C, Fucharoen S, Kole R. (2002b) Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides. Mol Pharmacol.; 62: 545-53.
• Taylor JK, Zhang QQ, Wyatt JR, Dean NM. (1999) Induction of endogenous Bcl-xS through the control of Bcl-x pre- mRNA splicing by antisense oligonucleotides. Nat Biotechnol.; 17: 1097-100.
• Vacek MM, Ma H, Gemignani F, Lacerra G, Kafri T, Kole R. (2003) High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA. Blood.; 101: 104-11.
• Wilton SD, Lloyd F, Carville K, Fletcher S, Honeyman K, Agrawal S, Kole R. (1999) Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides. Neuromuscul Disord.; 9: 330-8.