Targeted Macrophage CRISPR-Cas13 mRNA Editing in Immunotherapy for Tendon Injury

Targeted Macrophage CRISPR-Cas13 mRNA Editing in Immunotherapy for Tendon Injury

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 19 vom: 01. Mai, Seite e2311964
1. Verfasser: Wang, Shuo (VerfasserIn)
Weitere Verfasser: Xiao, Yao, Tian, Jian, Dai, Bo, Tao, Zaijin, Liu, Jingwen, Sun, Zhenyu, Liu, Xuanzhe, Li, Yanhao, Zhao, Gang, Cui, Yong, Wang, Fei, Liu, Shen
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article Cas13 RNP SPP1 macrophage targeting peritendinous adhesion RNA, Messenger Osteopontin 106441-73-0 Reactive Oxygen Species
Beschreibung
Zusammenfassung:© 2024 Wiley‐VCH GmbH.
CRISPR-Cas13 holds substantial promise for tissue repair through its RNA editing capabilities and swift catabolism. However, conventional delivery methods fall short in addressing the heightened inflammatory response orchestrated by macrophages during the acute stages of tendon injury. In this investigation, macrophage-targeting cationic polymers are systematically screened to facilitate the entry of Cas13 ribonucleic-protein complex (Cas13 RNP) into macrophages. Notably, SPP1 (OPN encoding)-producing macrophages are recognized as a profibrotic subtype that emerges during the inflammatory stage. By employing ROS-responsive release mechanisms tailored for macrophage-targeted Cas13 RNP editing systems, the overactivation of SPP1 is curbed in the face of an acute immune microenvironment. Upon encapsulating this composite membrane around the tendon injury site, the macrophage-targeted Cas13 RNP effectively curtails the emergence of injury-induced SPP1-producing macrophages in the acute phase, leading to diminished fibroblast activation and mitigated peritendinous adhesion. Consequently, this study furnishes a swift RNA editing strategy for macrophages in the inflammatory phase triggered by ROS in tendon injury, along with a pioneering macrophage-targeted carrier proficient in delivering Cas13 into macrophages efficiently
Beschreibung:Date Completed 09.05.2024
Date Revised 29.05.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202311964