Antisense Therapy of Hepatitis B Virus Infection: In Vivo Analyses in the Duck Hepatitis B Virus Model
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Infectious diseases in general and viral infections in particular can be viewed as acquired genetic diseases ( 1 , 2 ). At the molecular level, clinical signs and symptoms of viral infections are frequently caused by the expression or overexpression of the acquired genes. Based on this basic concept, such acquired genetic diseases should be amenable to treatment by a specific block of gene expression. Gene expression can be blocked at different levels by the following strategtes: sense strategy, antigene strategy, ribozymes, antisense strategy, and interfering peptrdes or proteins (Fig. 1 ).
Fig. 1. Principle of gene expression and strategies aimed at block of gene expression (1) sense strategy based on the binding of regulatory proteins, e g., transcription factors, by oligonucleotides, resulting in a block of transcription; (2) antigene strategy based on triple helix formation between oligonucleotides and double-stranded DNA, resulting in a block of transcription; (3) ribozymes resulting in specifically targeted degradation of mRNA, resulting in a block of translation, (4) antisense strategy based on binding of oligonucleotides to mRNA, resulting in a block of translation; (5) functional inactivation of proteins by binding to other proteins or peptides synthesized intracellularly after transduction of the specific coding sequences
