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  • Title: Highly sensitive inhibition of hTERT mRNA expression and telomerase activity by DNA-signal-peptide conjugates.
    Author: Kubo T, Bakalova R, Zhelev Z, Ohba H, Fujii M.
    Journal: Nucleic Acids Symp Ser (Oxf); 2005; (49):337-8. PubMed ID: 17150771.
    Abstract:
    In the present study, we investigated the antisense properties of conjugate oligonucleotides (ODNs) inhibiting human telomerase activity. Conjugate oligonucleotides assembled with signal peptides, artificially designed peptides, amines and sugars were synthesized by solid phase fragment condensation (SPFC) in sufficient yields. Conjugate ODNs showed a high resistance to nuclease degradation and sufficient binding affinity to target RNA, comparatively rapid and sufficient intracellular delivery and specific localization controlled by signal peptides (nuclear localization signals, NLS; nuclear export signals, NES). ODN-NLS conjugates demonstrated high antisense inhibitory effects against human telomerase activity into the nucleus (e. g, phosphorothioate conjugate inhibited the telomerase activity over 95%), whereas ODN-NES conjugates inhibited target mRNA expression into the cytoplasm.
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