Recent advances in gene therapy and gene-editing techniques offer the very real potential for successful treatment of neurological diseases. However, drug delivery constraints continue to impede viable therapeutic interventions targeting the brain due to its anatomical complexity and highly restrictive microvasculature that is impervious to many molecules. Realizing the therapeutic potential of gene-based therapies requires robust encapsulation and safe and efficient delivery to the target cells. Although viral vectors have been widely used for targeted delivery of gene-based therapies, drawbacks such as host genome integration, prolonged expression, undesired off-target mutations, and immunogenicity have led to the development of alternative strategies. Engineered virus-like particles (eVLPs) are an emerging, promising platform that can be engineered to achieve neurotropism through pseudotyping. This review outlines strategies to improve eVLP neurotropism for therapeutic brain delivery of gene-editing agents.
Keywords: MT: Delivery Strategies; blood-brain barrier; delivery systems; engineered virus-like particles; gene editing; neurological diseases; virus pseudotyping.
© 2024 The Author(s).