4.6 Article

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

Journal

ACS CHEMICAL BIOLOGY
Volume 17, Issue 2, Pages 292-298

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acschembio.1c00652

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This study reports 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 and presents an innovative approach for targeted delivery of siRNAs to B cell lymphomas.
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.

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