306Oi10 is a branched-chain ionizable lipidoid.1 It has been used in the generation of lipid nanoparticles (LNPs). It has strong surface ionization at pH 5, which is the pH in the late endosomal compartment, and a surface pKa value of 6.4 when encapsulating mRNA. LNPs containing 306Oi10 and encapsulating an mRNA reporter accumulate primarily in the mouse liver and those encapsulating erythropoietin increase serum erythropoietin levels in mice. LNPs containing 306Oi10 and encapsulating mRNA encoding the Cas9 nuclease (mCas9) and single-guide RNA targeting LoxP (sgLoxP) have been used to induce CRISPR-mediated gene editing in Ai9 mice that express a floxed STOP codon to prevent tdTomato expression.2
1.Hajj, K.A., Ball, R.L., Deluty, S.B., et al.Branched-tail lipid nanoparticles potently deliver mRNA in vivo due to enhanced ionization at endosomal pHSmall15(6)e1805097(2019) 2.Hajj, K.A., Melamed, J.R., Chaudhary, N., et al.A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivoNano Lett.20(7)5167-5175(2020)