Membrane Fusion-Mediated Loading of Therapeutic siRNA into Exosome for Tissue-Specific Application.
Adv Mater
; 36(33): e2403935, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38889294
ABSTRACT
Tissue-specific delivery of oligonucleotide therapeutics beyond the liver remains a key challenge in nucleic acid drug development. To address this issue, exploiting exosomes as a novel carrier has emerged as a promising approach for efficient nucleic acid drug delivery. However, current exosome-based delivery systems still face multiple hurdles in their clinical applications. Herein, this work presents a strategy for constructing a hybrid exosome vehicle (HEV) through a DNA zipper-mediated membrane fusion approach for tissue-specific siRNA delivery. As a proof-of-concept, this work successfully fuses a liposome encapsulating anti-NFKBIZ siRNAs with corneal epithelium cell (CEC)-derived exosomes to form a HEV construct for the treatment of dry eye disease (DED). With homing characteristics inherited from exosomes, the siRNA-bearing HEV can target its parent cells and efficiently deliver the siRNA payloads to the cornea. Subsequently, the NFKBIZ gene silencing significantly reduces pro-inflammatory cytokine secretions from the ocular surface, reshapes its inflammatory microenvironment, and ultimately achieves an excellent therapeutic outcome in a DED mouse model. As a versatile platform, this hybrid exosome with targeting capability and designed therapeutic siRNAs may hold great potential in various disease treatments.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Small Interfering
/
Exosomes
/
Liposomes
/
Membrane Fusion
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Mater
/
Adv. mater. (Weinheim Print)
/
Advanced materials (Weinheim Print)
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2024
Document type:
Article
Country of publication:
Alemania