Silence Therapeutics plc, AIM:SLN a leader in the discovery, delivery and development of novel RNA therapeutics for the treatment of serious diseases with unmet medical need, has told DirectorsTalk about significant in vivo CRISPR/Cas9 gene editing data. These data will be presented at the EuroTIDES 2016 meeting in Berlin, Germany.
Using its proprietary liver targeted lipid nanoparticle (LNP) to deliver the CRISPR/Cas9 components, Silence has confirmed the potential of its delivery platform for in vivo gene editing:
· Sustained down-regulation of two independent secreted liver gene products in blood serum was observed for over 200 days
· Serum levels of TTR protein were reduced by approximately 70%
· In the cross-controlled experimental cohort, serum levels of PCSK9 protein were reduced by approximately 55%
· Target levels in the groups treated with a guide RNA (gRNA) directed to a different gene were comparable to those of untreated animals
Ali Mortazavi, Chief Executive Officer of Silence Therapeutics, commented: “As in RNA interference, efficient payload delivery is critical in gene editing. We have leveraged our experience in RNA delivery systems to demonstrate that our LNP can be used for CRISPR/Cas9 applications. The pre-clinical biological activity that we have observed supports future in vivo clinical applications in the gene editing space, which was initially thought to be limited to ex vivo interventions. We have shown that our LNPs are suitable for the delivery of large cargos such as RNA CRISPR/Cas9 components, and we are discussing collaborations in this area with potential partners.”
Study details
The present experiment was designed as a preliminary proof-of-concept for the use of our optimised LNPs to co-deliver mRNA encoding Cas9 and gRNA targeting either the mouse TTR or PCSK9 genes. In vivo activity through gene-specific DNA disruption in mouse liver was measured by quantification of corresponding proteins in serum. Upon completion of the study, further data will become available.
