Lipid Nanoparticles for Broad-Spectrum Nucleic Acid Delivery

Hejdankova Zuzana; Vanek Vaclav; Sedlak FrantisekProchazka JanDiederichs AudreyKereiche SamiNovotna BarboraBudesinsky MilosBirkus GabrielGrantz Saskova KlaraCigler Petr

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Lipid Nanoparticles for Broad-Spectrum Nucleic Acid Delivery

机译：Lipid Nanoparticles for Broad-Spectrum Nucleic Acid Delivery

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Lipid nanoparticles (LNPs) are the most advanced nonviral modality for nucleic acid (NA) delivery, and have recently gained enormous attention in the fields of RNA therapeutics and vaccine development. Here, ionizable adamantane-based lipidoids named XMaNs, which circumvent the usual need for laborious optimization of LNP components for highly diverse types of NAs, are described. The non-toxic XMaN6 lipidoid is highly versatile in entrapment and delivery of siRNA, mRNA, plasmid DNA, and a cyclic dinucleotide. XMaN6-based LNPs efficiently deliver: 1) siRNA into human primary hepatocytes and cell lines that are hard-to-transfect; 2) mRNA into mouse liver; 3) plasmid DNA; 4) 2 ',3 '-cGAMP into cells and activated the cGAS-STING pathway three orders of magnitude more efficiently than 2 ',3 '-cGAMP alone. To our knowledge, such universality in delivering different NA types has not been previously described and can accelerate translation of LNPs into the clinic.

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《Advanced functional materials》 |2021年第47期|2101391.1-2101391.9|共9页
作者
Hejdankova Zuzana; Vanek Vaclav; Sedlak FrantisekProchazka JanDiederichs AudreyKereiche SamiNovotna BarboraBudesinsky MilosBirkus GabrielGrantz Saskova KlaraCigler Petr;
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Czech Acad Sci, Inst Organ Chem & Biochem, Flemingovo 2, Prague 16610 6, Czech Republic|Charles Univ Prague, Dept Genet & Microbiol, Prumyslova 595, Vestec 25250, Czech Republic|Res Ctr BIOCEV, Prumyslova 595, Vestec 25250, Czech Republic;

Czech Acad Sci, Inst Organ Chem & Biochem, Flemingovo 2, Prague 16610 6, Czech Republic;

Czech Acad Sci, Inst Organ Chem & Biochem, Flemingovo 2, Prague 16610 6, Czech Republic|Charles Univ Prague, Dept Genet & Microbiol, Prumyslova 595, Vestec 25250, Czech Republic|Res Ctr BIOCEV, Prumyslova 595, Vestec 25250, Czech Republic|Charles Univ PraCzech Acad Sci, Inst Mol Genet, Czech Ctr Phenogenom, Prumyslova 595, Vestec 25250, Czech Republic|Div BIOCEV, Lab Transgen Models Dis, Prumyslova 595, Vestec 25250, Czech RepublicCharles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Lab Struct Biol, Albertov 4, Prague 12801 2, Czech Republic;

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正文语种英语
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cyclic dinucleotides; DNA; drug delivery; lipid nanoparticles; RNA;

Lipid Nanoparticles for Broad-Spectrum Nucleic Acid Delivery

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