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Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo.

ABSTRACT: The efficient delivery of antisense oligonucleotides (ASOs) to the targeted cells and organs remains a challenge, in particular, in vivo. Here, we investigated the ability of a library of biodegradable lipid nanoparticles (LNPs) in delivering ASO to both cultured human cells and animal models. We first identified three top-performing lipids through in vitro screening using GFP-expressing HEK293 cells. Next, we explored these three candidates for delivering ASO to target proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA in mice. We found that lipid 306-O12B-3 showed efficiency with the median effective dose (ED50) as low as 0.034 mg·kg-1, which is a notable improvement over the efficiency reported in the literature. No liver or kidney toxicity was observed with a dose up to 5 mg·kg-1 of this ASO/LNP formulation. The biodegradable LNPs are efficient and safe in the delivery of ASO and pave the way for clinical translation.

SUBMITTER: Yang L

PROVIDER: S-EPMC7036716 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo.

Yang Liu L Ma Feihe F Liu Fang F Chen Jinjin J Zhao Xuewei X Xu Qiaobing Q

Molecular therapy. Nucleic acids 20200125

The efficient delivery of antisense oligonucleotides (ASOs) to the targeted cells and organs remains a challenge, in particular, in vivo. Here, we investigated the ability of a library of biodegradable lipid nanoparticles (LNPs) in delivering ASO to both cultured human cells and animal models. We first identified three top-performing lipids through in vitro screening using GFP-expressing HEK293 cells. Next, we explored these three candidates for delivering ASO to target proprotein convertase sub ...[more]

PMID: 32160706

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Dataset Information

Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo.

Publications

Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo.

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