Gene therapy, RNA-based drugs, and CRISPR in neuroprotection

Neurodegenerative diseases are associated with progressive neural malfunction, which is driven by common molecular pathologies that encompass protein aggregations, mitochondrial dysfunction, aberrant RNA metabolism and impaired intracellular clearance. Conventional treatments are largely symptomatic with no treatment of the underlying pathology. Gene therapies, RNA-based therapeutic platforms and CRISPR-based genome-editing technologies provide more targeted methods to regulate the pathological pathways and restore neuronal homeostasis. Nevertheless, these interventions can have transient, reversible or long-term effects instead of a consistent irreversible effect depending on the platform being used. Engineered viral vectors, particularly adeno-associated viruses, enable cell-type-specific and circuit-resolved delivery within the central nervous system. Although constrained by a limited packaging capacity (∼4.7 kb), innovations such as dual-vector systems and capsid engineering are expanding their functional utility. RNA therapeutics, such as antisense oligonucleotides, siRNA/miRNA and synthetic mRNA, provide reversible gene expression regulation, whereas CRISPR can be used to disrupt, correct or regulate the expression of specific genes. Together, these platforms constitute a multifaceted and evolving toolkit for neuroprotection, with the potential to modify disease progression in neurodegenerative disorders. However, most approaches remain at preclinical or early clinical stages, and further validation is required to establish long-term efficacy and safety.