Enhancement of Gene Knockdown on CD22-Expressing Cells by Chemically Modified Glycan Ligand–siRNA Conjugates

Autor:	Toshimasa Harumoto, Hiroto Iwai, Mari Tanigawa, Toshiko Kubo, Toshiyuki Atsumi, Kyoko Tsutsumi, Michio Takashima, Giuseppe Destito, Rachel Soloff, Kazuma Tomizuka, Corwin Nycholat, James Paulson, Keiji Uehara
Rok vydání:	2022
Předmět:	Polysaccharides Gene Knockdown Techniques Molecular Medicine General Medicine Oligonucleotides Antisense RNA Small Interfering Ligands Biochemistry
Zdroj:	ACS Chemical Biology. 17:292-298
ISSN:	1554-8937 1554-8929
DOI:	10.1021/acschembio.1c00652
Popis:	Extrahepatic targeted delivery of oligonucleotides, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), is an attractive technology for the development of nucleic acid-based medicines. To target CD22-expressing B cells, several drug platforms have shown promise, including antibodies, antibody-drug conjugates, and nanoparticles, but to date CD22-targeted delivery of oligonucleotide therapeutics has not been reported. Here we report the uptake and enhancement of siRNA gene expression knockdown in CD22-expressing B cells using a chemically stabilized and modified CD22 glycan ligand-conjugated siRNA. This finding has the potential to broaden the use of siRNA technology, opening up novel therapeutic opportunities, and presents an innovative approach for targeted delivery of siRNAs to B cell lymphomas.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::029757b45fdad86962ee3a057569240b https://doi.org/10.1021/acschembio.1c00652 Zobrazit plný text záznamu