フェリチンベースのsiRNA送達システムが膠芽腫治療に有望な結果を示す(Novel Ferritin-based siRNA Delivery System Shows Promise for Targeted Glioblastoma Therapy)

2025-02-20 中国科学院(CAS)

<関連情報>

• https://english.cas.cn/newsroom/research_news/life/202502/t20250227_902704.shtml
• https://www.science.org/doi/10.1126/sciadv.adr9266

膠芽腫における標的RNAi療法のためのsiRNAのリソソームからの脱出を促進する生物工学的タンパク質ナノキャリア Bioengineered protein nanocarrier facilitating siRNA escape from lysosomes for targeted RNAi therapy in glioblastoma

Yiliang Jin, Baoli Zhang, Jianru Li, Zhenxi Guo, […], and Kelong Fan
Science Advances  Published:19 Feb 2025

Abstract

RNA interference (RNAi) represents a promising gene-specific therapy against tumors. However, its clinical translation is impeded by poor performance of lysosomal escape and tumor targeting. This challenge is especially prominent in glioblastoma (GBM) therapy, necessitating the penetration of the blood-brain barrier (BBB). Leveraging the intrinsic tumor-targeting and BBB traversing capability of human H-ferritin, we designed a series of ferritin variants with positively charged cavity and truncated carboxyl terminus, termed tHFn(+). These nanocarriers respond to weak acid and disassemble in endosomal compartments, exposing the internal positive charges to facilitate the lysosomal escape of loaded small interfering RNA (siRNA). Functioning as universal siRNA nanocarriers, tHFn(+) significantly enhanced the uptake of different siRNAs and suppressed gene expressions associated with GBM progression. Furthermore, tHFn(+) traversed the BBB and targeted glioma in vivo by binding to its receptors (e.g., transferrin receptor 1). tHFn(+)-delivered siRNAs exhibited exceptional therapeutic effects against glioma in vivo, advancing RNAi therapeutics beyond GBM for the treatment of various diseases.