Open AccessLipid Nanoparticle Spherical Nucleic Acids for Intracellular DNA and RNA Delivery
Author(s) -
Andrew J. Sinegra,
Michael Evangelopoulos,
Jungsoo Park,
Ziyin Huang,
Chad A. Mirkin
Publication year - 2021
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.1c01973
Subject(s) - biodistribution , rna , nucleic acid , dna , liposome , intracellular , chemistry , spleen , messenger rna , microbiology and biotechnology , cytoplasm , biochemistry , biology , in vitro , immunology , gene
Lipid nanoparticle SNAs (LNP-SNAs) have been synthesized for the delivery of DNA and RNA to targets in the cytoplasm of cells. Both the composition of the LNP core and surface-presented DNA sequences contribute to LNP-SNA activity. G-rich sequences enhance the activity of LNP-SNAs compared to T-rich sequences. In the LNP core, increased cholesterol content leads to greater activity. Optimized LNP-SNA candidates reduce the siRNA concentration required to silence mRNA by 2 orders of magnitude compared to liposome-based SNAs. In addition, the LNP-SNA architectures alter biodistribution and efficacy profiles in mice. For example, mRNA within LNP-SNAs injected intravenously is primarily expressed in the spleen, while mRNA encapsulated by LNPs (no DNA on the surface) was expressed primarily in the liver with a relatively small amount in the spleen. These data show that the activity and biodistribution of LNP-SNA architectures are different from those of conventional liposomal SNAs and therefore potentially can be used to target tissues.