On Future's Doorstep: RNA Interference and the Pharmacopeia of Tomorrow

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2007 Dec 7

PMID 18060018

Citations 20

Authors

Alan M Gewirtz

Affiliations

Soon will be listed here.

Abstract

Small molecules and antibodies have revolutionized the treatment of malignant diseases and appear promising for the treatment of many others. Nonetheless, there are many candidate therapeutic targets that are not amenable to attack by the current generation of targeted therapies, and in a small but growing number of patients, resistance to initially successful treatments evolves. This Review Series on the medicinal promise of posttranscriptional gene silencing with small interfering RNA and other molecules capable of inducing RNA interference (RNAi) is motivated by the hypothesis that effectors of RNAi can be developed into effective drugs for treating malignancies as well as many other types of disease. As this Review Series points out, there is still much to do, but many in the field now hope that the time has finally arrived when "antisense" therapies will finally come of age and fulfill their promise as the magic bullets of the 21st century.

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References

Calin G, Croce C . Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol. 2006; 33(2):167-73. DOI: 10.1053/j.seminoncol.2006.01.010. View

Fattal E, Bochot A . Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA. Adv Drug Deliv Rev. 2006; 58(11):1203-23. DOI: 10.1016/j.addr.2006.07.020. View

Couzin J . Nobel Prize in Physiology or Medicine. Method to silence genes earns loud praise. Science. 2006; 314(5796):34. DOI: 10.1126/science.314.5796.34. View

Beltinger C, Saragovi H, Smith R, LeSauteur L, Shah N, DeDionisio L . Binding, uptake, and intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides. J Clin Invest. 1995; 95(4):1814-23. PMC: 295714. DOI: 10.1172/JCI117860. View

Bots M, Maughan S, Nieuwland J . RNAi Nobel ignores vital groundwork on plants. Nature. 2006; 443(7114):906. DOI: 10.1038/443906a. View

Casey B, Glazer P . Gene targeting via triple-helix formation. Prog Nucleic Acid Res Mol Biol. 2001; 67:163-92. DOI: 10.1016/s0079-6603(01)67028-4. View

Grunweller A, Hartmann R . RNA interference as a gene-specific approach for molecular medicine. Curr Med Chem. 2005; 12(26):3143-61. DOI: 10.2174/092986705774933489. View

Kim Y, Kim V . Processing of intronic microRNAs. EMBO J. 2007; 26(3):775-83. PMC: 1794378. DOI: 10.1038/sj.emboj.7601512. View

Rossi J . Ribozymes in the nucleolus. Science. 1999; 285(5434):1685. DOI: 10.1126/science.285.5434.1685. View

10.

Zamaratski E, Pradeepkumar P, Chattopadhyaya J . A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H. J Biochem Biophys Methods. 2001; 48(3):189-208. DOI: 10.1016/s0165-022x(01)00149-x. View

11.

Rivas F, Tolia N, Song J, Aragon J, Liu J, Hannon G . Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol. 2005; 12(4):340-9. DOI: 10.1038/nsmb918. View

12.

Terui Y, Furukawa Y, Sakoe K, Ohta M, Saito M . Expression of differentiation-related phenotypes and apoptosis are independently regulated during myeloid cell differentiation. J Biochem. 1995; 117(1):77-84. DOI: 10.1093/oxfordjournals.jbchem.a124725. View

13.

Brown K, Chu C, Rana T . Target accessibility dictates the potency of human RISC. Nat Struct Mol Biol. 2005; 12(5):469-70. DOI: 10.1038/nsmb931. View

14.

Parker J, Roe S, Barford D . Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. EMBO J. 2004; 23(24):4727-37. PMC: 535097. DOI: 10.1038/sj.emboj.7600488. View

15.

Spagnou S, Miller A, Keller M . Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid DNA. Biochemistry. 2004; 43(42):13348-56. DOI: 10.1021/bi048950a. View

16.

Carmell M, Hannon G . RNase III enzymes and the initiation of gene silencing. Nat Struct Mol Biol. 2004; 11(3):214-8. DOI: 10.1038/nsmb729. View

17.

Bitko V, Musiyenko A, Shulyayeva O, Barik S . Inhibition of respiratory viruses by nasally administered siRNA. Nat Med. 2004; 11(1):50-5. DOI: 10.1038/nm1164. View

18.

Martinez J, Patkaniowska A, Urlaub H, Luhrmann R, Tuschl T . Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell. 2002; 110(5):563-74. DOI: 10.1016/s0092-8674(02)00908-x. View

19.

Liao H, Wang J . Biomembrane-permeable and Ribonuclease-resistant siRNA with enhanced activity. Oligonucleotides. 2005; 15(3):196-205. DOI: 10.1089/oli.2005.15.196. View

20.

Wu Y, Yu L, McMahon R, Rossi J, Forman S, Snyder D . Inhibition of bcr-abl oncogene expression by novel deoxyribozymes (DNAzymes). Hum Gene Ther. 1999; 10(17):2847-57. DOI: 10.1089/10430349950016573. View