TCL065

TCL065, an ionizable cationic lipid (pKa = 6.3), is utilized in the creation of lipid nanoparticles (LNPs) for the delivery of mRNA and single-guide RNA (sgRNA) both in vitro and in vivo. When LNPs with TCL065 encapsulate sgRNA targeting the donor site of dystrophin exon 45, along with those targeting the splicing acceptor site of dystrophin exon 45, dystrophin expression is restored in myoblasts derived from induced-pluripotent stem (iPS) cells from Duchenne muscular dystrophy (DMD) patients. Additionally, TCL065-containing LNPs encapsulating mRNA encoding Cas9 nuclease, combined with those containing sgRNA targeting the Rosa26 locus, have been applied for CRISPR-mediated gene editing in mouse gastrocnemius muscle.