Human ribonuclease Dicer inhibition using RNA aptamers

The aim of this invention was to select RNA aptamers that specifically bind human ribonuclease Dicer, which is one of the main enzymes that take part in miRNA biogenesis and the biogenesis of other short regulatory RNAs, and then to find out if pre-selected molecules affect enzyme activity. Other aims of this solution include: 1) using RNA aptamers as ribonuclease Dicer competitive inhibitors; 2) using RNA aptamers that are allosteric ribonucle- ase Dicer inhibitors, 3) identifying RNA aptamers that are selective inhibitors of emergence of selected miRNAs.

REFERENCES (14)

Bartel D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2): 281-297.

Google Scholar

Blank M., Blind M., (2005) Aptamers as tools for target validation. Curr. Opin. Chem. Biol. 9(4): 336-42.

Google Scholar

Ellington A.D., Szostak J.W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 46(6287): 818-822.

Google Scholar

Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature 391(6669): 806-811.

Google Scholar

Haley B., Zamore P.D. (2004) Kinetic analysis of the RNAi enzyme complex. Nat. Struct. Mol. Biol. 11(7): 599-606.

Google Scholar

Hammond S.M., Bernstein E., Beach D., Hannon G.J. (2000) An RNA-directed nuclease mediates posttranscriptional gene silencing in Drosophila cells. Nature 404(6775): 293- 296.

Google Scholar

Macrae I.J., Zhou K., Li F., Repic A., Brooks A.N., Cande W.Z., Adams P.D., Doudna J.A. (2006) Structural basis for doublestranded RNA processing by Dicer. Science 311(5758): 195-198.

Google Scholar

Nimjee S.M., Rusconi C.P., Sullenger B.A. (2005) Aptamers: an emerging class of therapeutics. Annu. Rev. Med. 56: 555-583.

Google Scholar

Nykanen A., Haley B., Zamore P.D. (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107(3): 309-321.

Google Scholar

10.

Proske D., Blank M., Buhmann R., Resch A. (2005) Aptamers-- basic research, drug development, and clinical applications. Appl. Microbiol. Biotechnol. 69(4): 367-374.

Google Scholar

11.

Tuerk C., Gold L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968): 505-510.

Google Scholar

12.

White R.R., Sullenger B.A., Rusconi C.P. (2000) Developing aptamers into therapeutics. J. Clin. Invest. 106(8): 929- 934.

Google Scholar

13.

Yan A.C., Bell K.M., Breeden M.M., Ellington A.D. (2005) Aptamers: prospects in therapeutics and biomedicine. Front. Biosci. 10: 1802-1827.

Google Scholar

14.

Zhang K., Nicholson A.W. (1997) Regulation of ribonuclease III processing by double-helical sequence antideterminants. Proc. Natl. Acad. Sci. USA 94(25): 13437-13441.

Google Scholar

Submit your paper

Instructions for authors

eISSN:	2353-9461
ISSN:	0860-7796