1. Disulfide‐Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA
- Author
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Naoko Abe, Saki Kawaguchi, Hiroshi Abe, Daichi Fushihara, Azumi Ota, Iku Tanaka, Yasuaki Kimura, Yoshihiro Ito, Fumiaki Tomoike, Zhaoma Shu, Seiichi Tada, and Kosuke Nakamoto
- Subjects
Liposome ,010405 organic chemistry ,Oligonucleotide ,Chemistry ,Endosome ,media_common.quotation_subject ,Biological Transport ,General Chemistry ,General Medicine ,010402 general chemistry ,Endocytosis ,01 natural sciences ,Catalysis ,DNA, Antisense ,0104 chemical sciences ,Cell biology ,Cytosol ,Cytoplasm ,Humans ,Disulfides ,RNA, Small Interfering ,Internalization ,Intracellular ,media_common - Abstract
Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor-ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide-modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.
- Published
- 2019