Divergent transcription from lentiviral gene editing of cancer cells

We explored a gene editing approach to depleting ephrinB2 from colorectal cancer cells using an inducible lentiviral vector encoding a short hairpin (sh) RNA for ephrinB2 silencing via RNA interference. We discovered that lentiviral integration in the host DNA frequently drives divergent gene transcription generating antisense reads by forcing splicing and read-through into the host DNA resulting in expression of chimeric vector/host transcripts. Overall design: Examination of RNA expression in HT-29 derived cell clones (596 clones).