Therapeutic oligonucleotides

Diasio, R.B. and Zhang, R. (1997) Pharmacology of therapeutic oligonucleotides. Antisense Nucleic Acid Drug Dev., 7, 239-243. 

Metabolomics, Metabonomics and Metabolite Profiling 10 Ribozymes and RNA Catalysis 11 Protein-Nucleic Acid Interactions Structural Biology 12 Therapeutic Oligonucleotides... 

The rapid growth in publications on DNA triple helices is largely due to their widely recognised relevance to the development of therapeutic oligonucleotides. Indeed, triplex formation by site-specific interaction of an oligonucleotide with double helical DNA has been used to... 

Sanghvi Y S, Schulte M (2004). Therapeutic oligonucleotides The state-of-the-art in purification technologies. Curr. Opin. Drug. Discov. Devel. 7(6) 765-776. 

Kole R, Vacek M, Williams T (2004). Modification of alternative splicing by antisense therapeutics. Oligonucleotides. 14 65-74. 

Gilar M, Fountain K J, et al. (2003). Characterization of therapeutic oligonucleotides using liquid chromatography with on-line mass spectrometry detection. Oligonucleotides. 13 229-243. 

C., Keefe, A. D. (2006). 2 -Deoxy purine, 2 -0-methyl pyrimidine (dRmY) aptamers as candidate therapeutics. Oligonucleotides 16, 337-351. 

The first of only two therapeutic oligonucleotides that have been approved for human use as of writing is fomvirsen (Vitravene). It was approved by the FDA in 1998 for the local treatment of cytomegalovirus retinitis. This compound represents the original type of therapeutic... 

This chapter broadly describes the lead optimization activities relevant to the development of novel conjugate siRNA therapeutics for hepatic targets via subcutaneous administration. For specific information regarding other therapeutic oligonucleotide technologies (e.g., antisense, aptamer, CpG, anti-miR), specific nanoparticle-based delivery systems, or non-hepatic targeting, readers are directed elsewhere (Bennett and Swayze, 2010 Kole et al., 2012). 

In principle, all therapeutic oligonucleotides that enter cells will eventually be metabolized to individual monomeric forms and be subject to endogenous nucleotide salvage pathways and join endogenous nucleotide pools within any given cell. The actual extent and rate at which this occurs will rely... 

Hagedom, P., Yakimov, V., Ottosen, S., Kammler, S., Nielsen, N., Hog, A., et al. (2013). Hepatotoxic potential of therapeutic oligonucleotides can be predicted from their sequence and modification pattern. Nucleic Acid Ther, 23 (5), 302-310. 

Dioxide. The sulfur-transfer reagent 3//-l,2-benzodithiol-3-one 1,1-dioxide (2, eq 1) is widely used in the preparation of oligonucleoside phosphorothioates, which are especially valuable in the development of therapeutic oligonucleotides against various t)q)es of cancer and infectious diseases in humans. ... 

During chemical RNA synthesis, a number of undesired products may be formed. Under acidic conditions, for instance, bond migration may alter normal 3 -5 diesters to aberrant 2 -5 diesters, which are known to interfere with several biochemical activities, that is, their accidental presence in therapeutic oligonucleotides is likely to lead to unanticipated or undesired effects. 

Lin ZJ, Li W, Dai G. Application of LC-MS for quantitative analysis and metabolite identi-fieation of therapeutic oligonucleotides. J Pharm Biomed Anal. 2007 44 330-41. 

Ming, X., K. Carver, and L. Wu, Albumin-based nanoconjugates for targeted delivery of therapeutic oligonucleotides. Biomaterials, 34 7939-7949, 2013. 

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