Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteins.

Li, Yamin; Yang, Tao; Yu, Yingjie; Shi, Nicola; Yang, Liu; Glass, Zachary; Bolinger, Justin; Finkel, Isaac James et al. · Biomaterials · 2018

basic_science · Level V

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Abstract

Protein based therapeutics with high specificities and low off-target effects are used for transient and accurate manipulation of cell functions. However, developing safe and efficient carriers for intracellular delivery of active therapeutic proteins is a long-standing challenge. Here we report a combinatorial library of chalcogen (O, S, Se) containing lipidoid nanoparticles (LNPs) as efficient nanocarriers for intracellular delivery of negatively supercharged Cre recombinase ((-30)GFP-Cre) and anionic Cas9:single-guide RNA (Cas9:sgRNA) ribonucleoprotein (RNP) for genome editing. The structure-activity relationship between the lipidoids and intracellular protein delivery efficiencies was explored and it was demonstrated that the newly developed LNPs are effective for gene recombination in vivo.

Medical subject headings