TMTP1-Modified Small Extracellular Vesicles Target BRAF Mutation in Anaplastic Thyroid Cancer Reversing Vemurafenib Resistance With CRISPR/Cas9 Delivery

  • J Extracell Vesicles. 2025 Sep;14(9):e70170. doi: 10.1002/jev2.70170.
Shuo Zhang  1 ,  Zhenrong Ji  1 ,  Xiaoyu Cheng  2 ,  Yue Ma  3 ,  Mingliang Feng  4 ,  Dasheng Cai  1 ,  Tao Bai  1
Affiliations
  • 1. Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, China.
  • 2. Department of Anesthesiology, General Hospital of Northern Theater Command, Shenyang, China.
  • 3. Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
  • 4. Department of Endoscopy, the First Hospital of China Medical University, Shenyang, China.
PMID: 41002137 DOI: 10.1002/jev2.70170
Abstract

This study investigates a novel approach to overcome Vemurafenib resistance in BRAF-mutant Anaplastic thyroid carcinoma (ATC) using CRISPR/Cas9 gene editing and TMTP1-modified extracellular vesicles (TMTP1-sgBRAF-EVs). By knocking out the BRAF gene, the study elucidates Vemurafenib-induced Ferroptosis mechanisms involving lipid peroxidation and Reactive Oxygen Species (ROS) generation in ATC cells. The developed TMTP1-sgBRAF-EVs system demonstrates superior tumour-targeting and drug delivery capabilities, significantly enhancing Vemurafenib efficacy in both in vitro and in vivo models. This innovative combination of gene editing technology with a nanoparticle delivery system shows promising potential as a therapeutic strategy for treating aggressive BRAF-mutant ATC.

Keywords
BRAF mutation; CRISPR/Cas9 gene editing; Vemurafenib resistance; anaplastic thyroid carcinoma; extracellular vesicles; ferroptosis.
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