DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies

Xiao Huang; Jasper Z. Williams; Ryan Chang; Zhongbo Li; Eric Gai; David M. Patterson; Yu Wei; Wendell A. Lim; Tejal A. Desai

Here we explored using a natural polymer, DNA, as the surface scaffold for loading biomolecules onto particles. We demonstrated, through near surface-saturated biomolecule loading and precise ratiometric control of moiety loading, that hybridization-based thermodynamics can overcome limitations of traditional surface conjugation such as reduced efficiency of multi-step reactions, steric hindrance, and decay of functional groups. The increased loading density of surface biomolecules was found to be necessary to make particles capable of presenting antigens to robustly activate synNotch receptors in primary human T cells, and may also significantly enhance immune cell signaling where ligand clustering is required 10, 46 . We also show the versatility of this strategy by fabricating particles of different sizes, as well as compositions with different degradation profiles. This method can be applied to other formats of biomaterial functionalization (e.g. scaffolds and nonspherical particles)