Design and applications of modified oligonucleotides

Abstract

Oligonucleotides have a wide range of applications in fields such as biotechnology, molecular biology, diagnosis and therapy. However, the spectrum of uses can be broadened by introducing chemical modifications into their structures. The most prolific field in the search for new oligonucleotide analogs is the antisense strategy, where chemical modifications confer appropriate characteristics such as hybridization, resistance to nucleases, cellular uptake, selectivity and, basically, good pharmacokinetic and pharmacodynamic properties. Combinatorial technology is another research area where oligonucleotides and their analogs are extensively employed. Aptamers, new catalytic ribozymes and deoxyribozymes are RNA or DNA molecules individualized from a randomly synthesized library on the basis of a particular property. They are identified by repeated cycles of selection and amplification, using PCR technologies. Modified nucleotides can be introduced either during the amplification procedure or after selection.

Selection of a novel DNA thioaptamer against HER2 structure

“…Pharmacokinetic animal studies have shown that thioaptamers not only exhibit greatly prolonged half-life in blood, but also are rapidly dispersed to various tissues and cleared through the kidney within acceptable time [35]. To date, however, no thioaptamer against HER2 has been reported in literature.…”

Comparative Activity and Specificity of Antisense Oligodeoxynucleotides and Small Interfering RNA in an in vitro Ewing Sarcoma Model

“…Since they are known to inhibit the RNase H cleavage, the area of RNase H cut in the EWS part is reduced in comparison with the unmodified AS ODN. Then, the EWS gene is not down regulated [26][27][28][29]. The consequences of inhibited EWS gene expression in nontumour cells are still unknown.…”

Combinatorial selection and delivery of thioaptamers

“…Moreover, monothio-modified ONs (both DNA and RNA) can be synthesized enzymatically [5]. Various pharmacokinetic studies in animals have shown that phosphorothioate analogues are rapidly dispersed to various tissues and are cleared through the kidney within acceptable time periods [6].…”