Abstract
Background: Glioblastoma constitutes the most frequent and aggressive primary malignant brain tumor in adults. Despite the advances in its treatment, its prognosis remains very poor. Gene therapy has been proposed as a complementary treatment since it may overcome the problem of the blood-brain barrier for systemic therapies, allowing to target tumor cells and their tumor microenvironment locally, without affecting the normal brain parenchyma. In comparison with viral vectors, non-viral vectors became an attractive tool due to their reduced potential of biosafety risks, lower cost, higher availability, and easy storage.
Objective: In this article, we aimed to outline the current preclinical and clinical developments of non-viral delivery systems for therapeutic transgene delivery in malignant gliomas.
Conclusion: Non-viral vectors are efficient tools for gene delivery since they exhibit reduced non-specific cytotoxicity and can go through several modifications in order to achieve high tumor tropism and the ability to cross the blood-brain barrier to access the tumor mass. However, further evaluations in preclinical models and clinical trials are required in order to translate it into the neuro-oncology clinic.
Keywords: Glioblastoma, non-viral gene therapy, cationic lipids, dendrimers, dendrigrafts, polymeric micelles, poly (β-amino esters), sleeping beauty transposons.
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