Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 9, Issue 3, Pages 299-315Publisher
MDPI
DOI: 10.3390/ijms9030299
Keywords
modified siRNA; RNA interference; RNA-PNA chimeras; peptide nucleic acids; RNA
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The discovery of siRNAs as the mediators of RNA interference has led to an increasing interest in their therapeutic applications. Chemical modifications are introduced into siRNAs to optimize the potency, the stability and the pharmacokinetic properties in vivo. Here, we synthesize and test the effects of RNA-3'-PNA chimeras on siRNA functioning and stability. We demonstrate that the chemical modifications are compatible with the siRNA machinery, because all the PNA-modified siRNAs can efficiently mediate specific gene silencing in mammalian cells. Furthermore, we find that the modification on the sense strand of siRNA results in an increased persistence of the activity, whereas modification on both strands results in enhanced nuclease resistance in serum.
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