Enhancement of Gene Knockdown on CD22-Expressing Cells by Chemically Modified Glycan Ligand–siRNA Conjugates
Toshimasa Harumoto, Hiroto Iwai, Mari Tanigawa, Toshiko Kubo, Toshiyuki Atsumi, Kyoko Tsutsumi, Michio Takashima, Giuseppe Destito, Rachel Soloff, Kazuma Tomizuka, Corwin M. Nycholat, James C. Paulson, Keiji Uehara
Abstract
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.