Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material

Tanaka, Hiroki; Takata, Nae; Sakurai, Yu et al.

Pharmaceutics, 2021, 13(4), 544

Permalink : https://hdl.handle.net/2115/81744

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https://doi.org/10.3390/pharmaceutics13040544     122

論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/81744
タイトル
Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material
著者
Tanaka, Hiroki ; Takata, Nae ; Sakurai, Yu ; Yoshida, Tokuyuki ; Inoue, Takao ; Tamagawa, Shinya ; Nakai, Yuta ; Tange, Kota ; Yoshioka, Hiroki ; Maeki, Masatoshi ; Tokeshi, Manabu ; Akita, Hidetaka
著者名
Tanaka, Hiroki
著者名
Takata, Nae
著者名
Sakurai, Yu
著者名
Yoshida, Tokuyuki
著者名
Inoue, Takao
著者名
Tamagawa, Shinya
著者名
Nakai, Yuta
著者名
Tange, Kota
著者名
Yoshioka, Hiroki
著者名
Maeki, Masatoshi
e-Rad_Researcher
60311437
著者名
Tokeshi, Manabu
著者名
Akita, Hidetaka
言語
英語
キーワード
siRNA
antisense oligonucleotide
lipid nanoparticle
発行日
2021-04
出版者
MDPI
収録物名
Pharmaceutics
巻(号)
13(4)
ページ
544
抄録
The world-first success of lipid nanoparticle (LNP)-based siRNA therapeutics (ONPATTRO(R)) promises to accelerate developments in siRNA therapeutics/gene therapy using LNP-type drug delivery systems (DDS). In this study, we explore the optimal composition of an LNP containing a self-degradable material (ssPalmO-Phe) for the delivery of oligonucleotides. siRNA or antisense oligonucleotides (ASO) were encapsulated in LNP with different lipid compositions. The hepatic knockdown efficiency of the target genes and liver toxicity were evaluated. The optimal compositions for the siRNA were different from those for ASO, and different from those for mRNA that were reported in a previous study. Extracellular stability, endosomal escape and cellular uptake appear to be the key processes for the successful delivery of mRNA, siRNA and ASO, respectively. Moreover, the compositions of the LNPs likely contribute to their toxicity. The lipid composition of the LNP needs to be optimized depending on the type of nucleic acids under consideration if the applications of LNPs are to be further expanded.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3390/pharmaceutics13040544