Adenovirus vector-mediated delivery of the CRISPR-CasRx system enables gene knockdown with suppressed collateral activity.
- Open access
Adenovirus-delivered CRISPR-CasRx achieves targeted gene knockdown with minimal collateral RNA cleavage in vivo, reducing potential side effects.
- Why it matters: Collateral activity from Cas13 systems poses safety concerns for clinical applications, especially when high expression levels cause unintended RNA cleavage. Controlling Cas13 expression could mitigate these risks.
- What they did: Researchers developed adenovirus vectors carrying CasRx and demonstrated efficient, targeted gene knockdown in cell lines, cultured murine hepatic cells, and mice, with suppressed collateral activity compared to plasmid delivery.
- The result: The approach successfully reduced Pcsk9 and serum cholesterol levels in mice without disrupting other gene expressions or causing liver toxicity, enabling safer in vivo gene therapy.