306Oi10

306O_i10 is a biodegradable, branched chain lipidoid developed for RNA delivery in lipid nanoparticles (LNPs). Interestingly, the unbranched analog was 10-fold less effective in delivering luciferase mRNA in mice. The increased potency is thought to be due to increased cone-shaped structure and protonation at endosomal pH resulting in enhanced endosomal escape. 306O_i10 has been used to co-deliver three mRNAs (firefly luciferase, mCherry, and erythropoietin). The LNPs derived from 306O_i10 were not immunogenic or toxic to the liver.

References:

1) Hajj KA, Ball RL, Deluty SB, Singh SR, Strelkova D, Knapp CM, Whitehead KA. (2019) “Branched-Tail Lipid Nanoparticles Potently Deliver mRNA In Vivo due to Enhanced Ionization at Endosomal pH.” Small.  Feb;15(6):e1805097. doi: 10.1002/smll.201805097

2) Hajj KA, Melamed JR, Chaudhary N, Lamson NG, Ball RL, Yerneni SS, Whitehead, KA (2020) “A Potent Branched-Tail Lipid Nanoparticle Enables Multiplexed mRNA Delivery and Gene Editing In Vivo.” Nano Lett.  20, 5167−5175.