Enhanced CRAd activity using enhancer motifs driven by a nucleosome positioning sequence.

ABSTRACT: Cancer development involves changes driven by the epigenetic machinery, including nucleosome positioning. Recently, the concept that adenoviral replication may be driven by tumor specific promoters (TSPs) gained support, and several conditionally replicative adenoviruses (CRAd) exhibited therapeutic efficacy in clinical trials. Here, we show for the first time that placing a nucleosome positioning sequence (NPS) upstream of a TSP combined with Wnt-responsive motifs (pART enhancer) enhanced the TSP transcriptional activity and increased the lytic activity of a CRAd. pART enhanced the transcriptional activity of the gastrointestinal cancer (GIC)-specific REG1A promoter (REG1A-pr); moreover, pART also increased the in vitro lytic activity of a CRAd whose replication was driven by REG1A-Pr. Th

SUBMITTER: Bravo S 

PROVIDER: S-EPMC3702098 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature