Enhanced Diagnostic Tools
The sequencing of the human genome provides various new tools and new opportunities for researches of life-science in the 21st century. In the context of the post-genome-sequencing era, the development of a general technology to regulate the targeted gene expression is highly important. Based on the fundamental features of the strict nucleobase recognition by means of Watson-Crick and Hoogsteen (reverse-Hoogsteen) hydrogen bondings, nucleic acids form duplex and triplex structures (Fig. 1). The oligonucleotides with high and sequence-specific binding affinity to single-stranded (ss) RNA and/or doublestranded (ds) DNA could serve as promising materials in antisense and/or antigene methodology (Fig. 2) not only for potential genomic drugs discovery but also for various diagnostic and biological applications. The oligonucleotides for an antisense and/or antigene application should fulfill some criteria such as (i) high-affinity and sequence selectivity towards ssRNA and/or dsDNA targets, (ii) stability towards enzymatic
hydrolysis, and (iii) efficient preparation on a DNA synthesizer, and so on. Due to the instability under physiological conditions of natural oligonucleotides, numerous artificial nucleoside (oligonucleotide) analogs have been developed and their utilization in antisense or antigene strategy has been tried.1–10 Recently, the first antisense drug for CMV retinitis using a phosphorothioate oligonucleotide (S-oligo) was approved by FDA.11 However, the phosphorothioate modification was known to decrease the binding affinity of the oligonucleotides towards the target sequences, and to show a nonspecific interaction with some biomolecules in a cell.9 Therefore, further chemical innovations are still desired for development of ideal antisense and/or antigene oligonucleotides.
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