Oligonucleotides therapeutic applications

The potential of the chemically modified nucleic acid molecules has been proven by in vitro studies however, the in vivo therapeutic applicability of these molecules seems to be unsatisfactory because of their possible toxic effects (largely unknown) and adverse bioavailability. In this view, both antisense and transfection technologies require reliable and efficient systems for their delivery into target cells. On the basis of this consideration, the development of an efficient nucleic acid delivery system represents one of the key steps for these therapeutic agents, which are necessary for a practical clinical utilization of natural or unnatural oligonucleotides. 

Orr, R. and O Neill, C. 2000. Patent review therapeutic applications of antisense oligonucleotides, 1999-2000. 

Mann MJ, Dzau VJ. Therapeutic applications of transcription factor decoy oligonucleotides, J Clin Invest 2000 106 1071-1075. 

Figure 42. PCT/EPO patents and national patents 1996-1998 sorted by therapeutic applications. Other includes Treatment of bacterial infections or wounds and oligonucleotides used as immune response modifiers.

Fichou, Y., Ferec, C. (2006). The potential of oligonucleotides for therapeutic applications. Trends Biotechnol 24, 563-570. 

Aptamers are highly structured, single-stranded RNA or DNA oligonucleotides that have been selected for their ability to bind target proteins with high affinity and selectivity, and which therefore possess numerous therapeutic applications. The process for selection is called SELEX (systematic evolution of ligands by exponential enrichment) and usually relies on an immobilised... 

Boranophosphate linkages have been of interest because they mimic natural DNA, and may have potential in diagnostic and therapeutic applications (boron neutron capture therapy). Boranophosphate-modified siRNA has been shown to possess potent gene-silencing properties compared to the unmodified siRNA. Two novel methods have been reported for the synthesis of boranophosphate oligonucleotides, one using phosphoramidite chemistry, the other boranophosphotriester chemistry. Dinucleoside boranophosphates and a-borano nucleoside triphosphates have also been described. " ... 

Based on the efforts of these pioneers in NAD research, various NAD concepts have been presented. In this review issue, various types of NADs are introduced, and the recent status of NAD research is summarized by leaders in the field. This issue focuses on the following six aspects of NAD (1) antisense ohgonucleotides, (2) decoy DNA, (3) CpG-oligonucleotides, (4) aptamers, (5) NAD delivery, and (6) therapeutic applications. They have been involved in innovating new, particularly noteworthy synthetic routes for stereocontrolled synthesis of OPTs. 

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