ABSTRACT
Hepatitis B virus (HBV) is responsible for > 350 million cases of chronic hepatitis B worldwide and 1.2 million deaths each year. To explore the use of ribozymes as a novel therapy for HBV infection, nuclease-resistant ribozymes that target highly conserved regions of HBV RNA were screened in cell culture. These synthetic ribozymes have the potential to cleave all four major HBV RNA transcripts and to block the HBV lifecycle by cleavage of the pregenomic RNA. A number of the screened ribozymes demonstrate activity in cell culture systems, as measured by decreased levels of HBV surface antigen, HBV e antigen and HBV DNA. In addition, a lead anti-HBV ribozyme maintains activity against a lamivudine-resistant HBV variant in cell culture. Treatment of HBV transgenic mice with lead anti-HBV ribozymes significantly reduced viraemia compared with saline-treated animals and was as effective as treatment with lamivudine. In conclusion, the therapeutic use of a ribozyme alone or in combination with current therapies (lamivudine or interferons) may lead to improved HBV therapy.
Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Hepatitis B virus/drug effects , Hepatitis B/drug therapy , RNA, Catalytic/pharmacology , RNA, Catalytic/therapeutic use , Animals , DNA, Viral/metabolism , Endonucleases/pharmacology , Hepatitis B/virology , Hepatitis B Surface Antigens/metabolism , Hepatitis B e Antigens/metabolism , Hepatitis B virus/genetics , Humans , Lamivudine/pharmacology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microbial Sensitivity Tests/methods , RNA, Catalytic/metabolism , RNA, Viral/metabolism , Tumor Cells, CulturedABSTRACT
Randomly assigned 44 outpatient Ss, enrollees of the George Washington University Health Plan, a Health Maintenance Organization (HMO), to one of three treatment modalities: (1) a cognitive behavior therapy group; (2) a traditional process-oriented interpersonal group; and (3) cognitive behavior therapy in an individual format. All Ss were referred by their physicians to the HMO Mental Health Practice for treatment for anxiety and/or depression. Beck's Depression Inventory, Speilberger's State-Trait Anxiety Inventory and Gay and Galassi's Adult Self-Expression Scale (an assertion measure) were administered pre- and post-treatment to all Ss. A subsample of these Ss also were rated pre- and post-treatment on the Hamilton Rating Scale for Depression by experienced clinicians blind to the treatment groups. All three experimental groups significantly improved on all dependent measures from pre- to post-treatment, and no differential treatment effects were found.