In this preclinical study, the safety and effectiveness of CRISPR-Cas9 genome editing technology for the long-term treatment of essential hypertension were evaluated in animal models. Through targeting the key genes involved in hypertension pathogenesis (ACE, AGT and NR3C2) by delivering nanocarriers encapsulating CRISPR constructs, a sustained and significant systolic blood pressure reduction (>32 mmHg) was observed up to 16 weeks after the treatment. Apart from hemodynamic parameter stabilization, this approach resulted in 51% improvement of glomerular filtration rate, two-fold sodium excretion and 68% reduction of proteinuria. Histological evaluation showed 66-77% reduction of target organ damage (kidney, heart, and blood vessels). Gene editing efficiency in kidney tissue was 92.4% and off-target effects were quantified at less than 0.15%. These findings report the therapeutic potential of this technology as a single-dose, long-term therapeutic strategy that can reduce the global burden of uncontrolled hypertension, though future studies should be aimed at tissue delivery optimization and long-term toxicity testing.