Parkinson’s disease (PD) remains a formidable challenge in neurology, with current therapies offering only symptomatic relief. The failure of intraputamenal glial cell line-derived neurotrophic factor (GDNF) infusion in Phase II trials (NCT01621581) underscores the limitations of invasive delivery and poor tissue penetration [1], while systemic GDNF administration is ineffective due to its inability to cross the blood–brain barrier (BBB) [2]. To address these challenges, I propose a novel, non-invasive strategy: exosomes engineered with rabies virus glycoprotein (RVG) for targeted delivery of GDNF mRNA to dopaminergic neurons in the substantia nigra (Fig. 1).