AAV-Containing Exosomes as a Novel Vector for Improved Gene Delivery to Lung Cancer Cells

Suicide gene
DOI: 10.3389/fcell.2021.707607 Publication Date: 2021-08-13T14:09:17Z
ABSTRACT
Lung carcinoma is the most common type of cancer and leading cause cancer-related death worldwide. Among numerous therapeutic strategies for treatment lung cancer, adeno-associated virus (AAV)-mediated gene transfer has been demonstrated to have potential effectively suppress tumor growth or reverse progression disease in a number preclinical studies. AAV vector safety profile; however, relatively low delivery efficacy particular subtypes limited its prospective clinical translation. Exosomes are nanosized extracellular vesicles secreted from nearly all known cell types. membrane-enclosed structure carrying range cargo molecules efficient intercellular functional entities, thus considered as superior drug delivery. In present study, we developed novel strategy produce purify AAV-containing exosomes (AAVExo) AAV-packaging HEK 293T cells. The cellular uptake capacity assisted enhanced entry into cells protected antibody neutralization, which was serious challenge vivo application. We tested list lines representing non-small-cell small-cell found that AAVExo apparently improved efficiency compared conventional vector. Our vitro results were supported xenograft rodent model. Additionally, evaluated presence neutralizing on AAVExo-mediated not impacted, while vectors significantly blocked by antibody. Taken together, established an methodology purification, purified largely with remarkable resistance neutralization.
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