Targeted AAV Gene Therapy for Triple-Negative Breast Cancer: Anti-EGFR Monoclonal Antibody-Conjugated Exosomes

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, high recurrence, and lack of HER2, progesterone, and estrogen receptors, making therapeutic targeting challenging. This study explores a novel gene therapy targeting mitochondria, which disrupts the inner mitochondrial membrane (IMM) potential, inducing cell death and suppressing tumor growth. While adeno-associated virus (AAV) is an effective, well-characterized gene delivery vector, immunogenicity limits its safety and efficacy. This study evaluates AAV-mediated delivery of the mLumiOpto gene therapy, utilizing nanoparticles and monoclonal antibodies for precision targeting of TNBC cells. mLumiOpto was delivered via anti-EGFR monoclonal antibody-tagged exosome-associated AAV (mAb-Exo-AAV). In vitro and in vivo experiments confirmed the expected size, morphology, specific binding to TNBC cells, cytotoxicity, and no off-target effects. These results suggest mAb-Exo-AAV delivery of mLumiOpto as a promising targeted TNBC therapeutic.