ADVANCED ENGINEERING APPROACHES FOR TARGETED GENE THERAPY DELIVERY ACROSS THE BLOOD–BRAIN BARRIER

Abstract

Background: The blood-brain barrier (BBB) is a significant barrier to effective delivery of gene therapy molecules into the central nervous system (CNS). Conventional therapeutic systems tend to show minimal BBB entry, minimal neuron specificity, rapid systemic elimination and lack of long term therapeutic retention.

Objective: This paper conducts an assessment of the modern methods of engineering that aim at enhancing focused delivery of gene therapy across the BBB in order to curb neurological conditions.

Methodology: Recent preclinical and translational studies of viral and non-viral delivery systems, nanoparticle engineering, receptor-mediated transport systems and BBB modulation technologies were thoroughly reviewed and compared to analyze in detail the relevant studies.

Findings: AAV9 vectors that had been engineered showed improved neuron transduction and better CNS biodistribution in comparison to the standard viral systems. Formulations of lipid nanoparticles enhancers were effective in stabilization of nucleic acid and decreased immunogenicity in systemic delivery. BBB disruption using focused ultrasound increased the ability of targeted therapy especially at the localized sites in murine models by 45-60 percent and receptor-targeted nanocarrier proved significantly more effective in transcytosis and neuronal uptake of biopsychtropic drugs. Almost 40 percent functional improvement in neuronal survival and neuroinflammatory markers was also reported with specific CNS delivery and functional studies of therapeutic interests.

Conclusion: State of the art engineering modalities have contributed largely to the accuracy, effectiveness and therapy capability of BBB-targeted gene delivery systems. However, to seek neurotherapeutic engagement in the future, long-term safety optimization, specificity, scalability of manufacturing, and clinical translation are crucial.