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Get Antisense Therapeutics 2nd edition (Methods in Molecular PDF

By M. Ian Phillips (Editor)

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Work is currently being done to engineer DNAzymes, which should be more stable than their ribozyme RNA counterparts (33). One benefit of exogenous ribozyme delivery in vivo is that the immune system is fairly tolerant of foreign RNA molecules (34). The other method for delivering ribozymes, endogenous expression of the ribozyme, is most often accomplished using viral vectors; however, plasmid vectors may also be used. Both retroviral and DNA viral vectors have been used. Expression cassettes can be designed to carry cell type–specific or conditional transcription initiation sites, as well as to include reporter proteins.

Furthermore, the perfluorobutane gas is an effective cell membrane fluidizer. The potential advantages of microbubble carrier delivery include minimal additional vessel injury from delivery, no resident polymer to degrade leading to eventual inflammation, rapid bolus delivery, and highly feasible repeated delivery. In addition, the potential for perfluorocarbon gas microbubble carriers (PGMCs) to deliver to vessel regions both proximal and distal to stents in vessels suggests that this mode of delivery will be excellent as an adjuvant to a variety of catheter and coated-stent delivery techniques.

Dose-response experiments revealed that the IC50 value for the siRNA was about 100-fold lower than that of the ASODNs (83). The effect of siRNA is also longer lasting than of AS-ODNs because siRNAs are more stable in fetal calf serum, human plasma, and cell cultures (84). By contrast, Vickers et al. (87) reported that optimized RNaseH-dependent oligonucleotides and siRNAs are comparable in terms of potency, maximal effectiveness, sequence specificity, and duration of action. An independent combinatorial effect of AS-ODNs and siRNAs has been observed when siRNA was coadministered with nonhomologous antisense oligonucleotides, targeting distant regions of the same mRNA (88).

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