| Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis. The latter can lead to end-stage liver failure and hepatocellular carcinoma. HBV possesses a very small partially double-stranded genome of 3.2 kb. Constrained by its size, the virus uses overlapping shifted reading frames to generate the full complement of proteins. Regulated by the core promoter, transcription of this DNA produces pregenomic and precore messenger RNAs (mRNAs), from which hepatitis B e/c (HBe/c) antigens and polymerase proteins are translated. The pregenomic RNA is also packaged into core particles and serves as a template for DNA replication. The terminal redundant regions of the pregenomic RNA contain functional elements such as direct repeats, an encapsidation signal, and a polyadenylation signal that play essential roles for HBV replication. Because of the importance of these regions, agents directed against these sites of pregenomic RNA have the potential for substantial inhibition of HBV gene expression and replication. RNA, as an intermediate in the production of every gene encoded protein and the genetic material of many pathogenic viruses, presents an attractive target for both biological and therapeutic manipulation. Despite its extensive involvement in living systems, its chemical diversity based on four units is relatively low compared with protein. This provides the opportunity for a generic approach to targeting with specificity based on primary structure rather than complex higher order structures. This form of recognition occurs naturally in complementary nucleic acids, due to an ability to bind their single stranded target through Watson-Crick interactions. The most established nucleic acid based approach to gene suppression at the RNA level is through antisense oligodeoxynucleotides(ASODN).These compounds form heteroduplex with target RNA which are thought to either block its function or mediate its destruction by activation of RNase H. Alternatively; RNA can be targeted by catalytic RNA such as the hammerhead ribozyme. Ribozymes have the advantage of being equipped with their own RNA cleavage apparatus and are therefore independent of host nuclear protein activity. At present, the utility of ribozyme oligonucleotides is restricted by the relatively difficulty synthesizing active molecules with sufficient resistance to nuclease degradation. Recently the power of in vitro selection has been used to evolve catalytic DNA sequences with RNA cleavage specificity and activity revalling the very best ribozymes, while maintaining the more robust chemistry of an ASODN. These deoxyribozymes or DNAzymes have tremendous potential as gene suppression agents for both target validation and therapeutic applications. A number of studies evaluating the biological activity of these compounds have shown promising results. However, as with other oligonucleotide based strategies, future exploitation of this approach may depend on accessory technology to assist with the accessibility of a target which is folded by its own secondary structure and hidden within the intracellular compartment. The use of deoxyribozymes as inhibitory molecules has at least three potential modes of actions: 1) as true ribonucleases; 2) as antisense molecules; 3) as DNA-RNA substrates for endogenous RNase H cleavage.Our research is to design and synthesize thosthorothioate 10-23DRz (DRz-S) and 10-23DRz specific to HBV pre-C/C gene ORFA2031. Observe the inhibition effects of 10-23DRz-S and 10-23DRz on the expression of HBV gene in HepG2.2.15 cells. Results are the expression of HBV gene was remarkable depressed after 2.2.15 cells transfected by DRz-S and DRz. The maximum inhibition was 93.75% and 90.26%; The inhibition was maintained for 96 hours; The inhibition time of DRz-S was longer than that of DRz, the maximum inhibition of DRz-S was lower than of DRz,; The efficiency of inhibiting HBsAg and HBeAg in 2.2.15 cells by DRz-S , DRz was higher than that by antisense oligoncleotides for the same target genes. Has no remarkable effec...
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