Fig. 1: Synthetic methodology of Branched ENdosomal Disruptor (BEND) ionizable lipid platform. | Nature Communications

Fig. 1: Synthetic methodology of Branched ENdosomal Disruptor (BEND) ionizable lipid platform.

From: Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein complex for hepatic gene editing and T cell engineering

Fig. 1

a Synthetic scheme to generate terminally branched epoxides of various lengths. Bromoalkenes undergo Cu-catalyzed C-C coupling with branched Grignard caps to form branched alkenes. The bromoalkene can be generated by a mono E2 reaction with a dibromoalkane and tert-butoxide. The terminally branched alkenes then undergo mCPBA-mediated epoxidation to form the terminally branched epoxides. b SN2 reaction with the 494 core and the linear or terminally branched epoxides to form the linear or BEND 494-core ILs (right). c Abbreviation scheme for the ILs. d Schematic of microfluidic formulation of linear or BEND LNPs. e BEND ILs facilitate greater endosomal disruption leading to increased hepatic mRNA translation. d, e were created in BioRender. Hamilton, A. (2024) https://BioRender.com/a46b016.

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