Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 50, Pages 46585-46590Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b17749
Keywords
mRNA delivery; CRISPR/Cas9 genome editing; cell-selective delivery; lipid nanoparticles; sialic acid
Funding
- National Key Research and Development Program of China [2017YFA0208100, 2018YFE0200800]
- National Natural Science Foundation of China [21778056, 21522509, 21874152, 21790390, 21790391]
- Beijing Normal University [312232109]
- Beijing National Laboratory for Molecular Sciences (BNLMS)
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Messenger RNA (mRNA) represents an emerging class of nucleic acid therapeutics for genome editing and genetic disease treatment. Delivering exogenous mRNA selectively to cells, however, remains a main challenge to broaden the biomedical application of mRNA and develop targeted gene therapy. Herein, we report cell-selective mRNA delivery and CRISPR/Cas9 genome editing by modulating the interface of phenylboronic acid (PBA) derived lipid nanoparticles (NPs) and cellular surface sialic acid (SA). We design a cationic lipid featuring a PBA group, PBA BADP, to self-assemble with mRNA into nanoparticles via electrostatic interactions. Importantly, these nanoparticles present free PBA groups on their surface, showing an enhanced cellular uptake by SA-overexpressing cancer cells via the interfacial PBA/SA interaction. It is shown that PBA-BADP/mRNA NPs transfection results in 300 times higher luciferase reporter gene expression in cancer cells than that in noncancer cells. Moreover, we demonstrate that the delivery of tumor suppressor p53 mRNA using PBA-BADP selectively prohibits cancer cell growth, while PBA-BADP/Cas9 mRNA NPs delivery knocks out gene expression of HeLa cancer cells in a much higher efficiency than noncancer cells. We believe these findings could further extend the modulation of PBA and cellular SA interface to advance mRNA delivery and genome editing for new gene therapy.
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