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1.  Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs 
Artificial DNA, PNA & XNA  2010;1(1):17-26.
Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma. Current treatment options have limited efficacy and chronic HBV infection is likely to remain a significant global medical problem for many years to come. Silencing HBV gene expression by harnessing RNA interference (RNAi) presents an attractive option for development of novel and effective anti HBV agents. However, despite significant and rapid progress, further refinement of existing technologies is necessary before clinical application of RNAi-based HBV therapies is realized. Limiting off target effects, improvement of delivery efficiency, dose regulation and preventing reactivation of viral replication are some of the hurdles that need to be overcome. To address this, we assessed the usefulness of the recently described class of altritol-containing synthetic siRNAs (ANA siRNAs), which were administered as lipoplexes and tested in vivo in a stringent HBV transgenic mouse model. Our observations show that ANA siRNAs are capable of silencing of HBV replication in vivo. Importantly, non specific immunostimulation was observed with unmodified siRNAs and this undesirable effect was significantly attenuated by ANA modification. Inhibition of HBV replication of approximately 50% was achieved without evidence for induction of toxicity. These results augur well for future application of ANA siRNA therapeutic lipoplexes.
doi:10.4161/adna.1.1.11981
PMCID: PMC3109439  PMID: 21687523
altritol; siRNA; RNAi; HBV; lipoplex; non viral vector
2.  Direct observation of two cyclohexenyl (CeNA) ring conformations in duplex DNA 
Artificial DNA, PNA & XNA  2010;1(1):2-8.
Cyclohexene Nucleic Acids (CeNA), in which the 2′-deoxyribofuranose ring of the DNA building blocks is substituted by a cyclohexenyl ring, were designed as potential mimics of natural nucleic acids for antisense and, later, for siRNA applications. CeNA units, in contrast to HNA (hexitol nucleic acid) building blocks, show more flexibility at the level of the C2′–C3′ bond due to the possibility of the cyclohexenyl moiety to adopt different conformations. In order to analyze the influence of CeNA residues onto the helix conformation and hydration of natural nucleic acid structures and to verify the cyclohexenyl ring conformation, a cyclohexenyl-thymine building block was incorporated into the non-self-complementary sequence d(GCG(xT)GCG)/d(CGCACGC) with (xT) a cyclohexene residue. The crystal structure of this sequence has been determined to a resolution of 1.17 Å and contains two duplexes in the asymmetric unit. The global helices belong to the B-type family and the conformations of the cyclohexenyl rings in both duplexes are different. The cyclohexene ring adopts as well the 2H3-conformation (similar to C2′-endo) as the 3H2-conformation (similar to C3′-endo). The crystal packing is stabilized by cobalt hexamine residues and triplet formation.
doi:10.4161/adna.1.1.10952
PMCID: PMC3109440  PMID: 21687521
cyclohexene nucleic acids; CeNA; cobalt hexamine; triplet formation; ring conformation

Results 1-2 (2)