Fig. 1: LNPs design to target high affinity conformation of α4β7 integrin.

a Illustration of the generation of LNPs using microfluidics. The ionizable lipid facilitates short interfering RNA (siRNA) encapsulation through its positive charge at low pH. b Overview of the different domains of the mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1)–Fc fusion protein. c Overview of the fusion strategy. The different domains of the wild-type MAdCAM-1 are shown. Only the integrin-binding domains D1 and D2 are used. D1D2 is fused to the hinge of rat IgG2a with a flexible linker. d Schematic drawing depicting the conjugation strategy of the MAdCAM-1–Fc to the LNPs. The RG7 linker (mAb against rat IgG2a) is chemically conjugated with the LNPs to the maleimide group in the lipid DSPE-PEG-maleimide. RG7 readily binds the MAdCAM-1–Fc by antibody affinity. e LNP targeting to HA α4β7 integrin. CCL25 induces the integrin conformational change. Reprinted by permission from Springer Nature Customer Service Centre GmbH: Springer Nature, Nature Nanotechnology, from Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics, Dammes, N., Goldsmith, M., Ramishetti, S. et al., © 2021.