9KAY
Bioengineered protein nanocarrier facilitating siRNA escape from lysosomes for targeted RNAi therapy in glioblastoma
This is a non-PDB format compatible entry.
Summary for 9KAY
| Entry DOI | 10.2210/pdb9kay/pdb |
| EMDB information | 62216 |
| Descriptor | Ferritin heavy chain, N-terminally processed (1 entity in total) |
| Functional Keywords | bioengineered ferritin, lysosomal escape, sirna delivery, glioblastoma targeted therapy, egfr and tert, metal transport |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 24 |
| Total formula weight | 448155.94 |
| Authors | |
| Primary citation | Jin, Y.,Zhang, B.,Li, J.,Guo, Z.,Zhang, C.,Chen, X.,Ma, L.,Wang, Z.,Yang, H.,Li, Y.,Weng, Y.,Huang, Y.,Yan, X.,Fan, K. Bioengineered protein nanocarrier facilitating siRNA escape from lysosomes for targeted RNAi therapy in glioblastoma. Sci Adv, 11:eadr9266-eadr9266, 2025 Cited by PubMed 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. PubMed: 39970222DOI: 10.1126/sciadv.adr9266 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (1.73 Å) |
Structure validation
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