Expression data from transgenic mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84429 | GEO | 2016/07/15
SECONDARY ACCESSION(S): PRJNA329136
REPOSITORIES: GEO
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Project description:Approved chronic hepatitis B (CHB) therapies rarely result in functional cure, as they fail to permanently silence all transcriptionally active hepatitis B virus (HBV) DNA. CRMA-1001 employs an optimized epigenetic silencer that represses viral transcription through targeted deposition of DNA methylation on episomal and integrated HBV DNAs. In HBV mouse models, a single dose of CRMA-1001 produced >3 log10 reductions in viral biomarkers, which correlated with de novo methylation of HBV DNA. Three doses resulted in up to 90% of animals with undetectable hepatitis B surface antigen (HBsAg) and HBV DNA by 6 months post-treatment. In non-human primates, CRMA-1001 induced transient liver transaminase elevations only at the highest dose tested. Expression and DNA methylation profiling revealed no detectable unintended targets in the human genome. These findings support the initiation of clinical development of CRMA-1001 as a finite treatment course with the potential for functional cure in individuals living with CHB.
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