Published September 1, 2025 | Version v1
Journal article Open

CRISPR-Cas9 gene editing for the long-term control of essential hypertension: preclinical advances and clinical perspectives

Authors/Creators

  • 1. Doctor of medical sciences, Associate professor of the Department of Neurology, Child Neurology and Medical Genetics, Tashkent State Medical university, Uzbekistan
  • 2. Doctor of medical Sciences, Professor, Head of the Department of Pediatrics N.2, Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
  • 3. PhD, Assistant at the Department of Otorhinolaryngology, Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
  • 4. Doctor of Chemistry, Professor, Termez State Pedagogical Institute, Uzbekistan.
  • 5. Department of propaedeutics of children's diseases, Tashkent State Medical university, Tashkent, Uzbekistan
  • 6. PhD, Associate Professor at the Jizzakh Polytechnic Institute, Uzbekistan
  • 7. Teacher of the Department of Individual Wrestling of Urganch State University, 14, Kh.Alimdjan str, Urgench city, 220100, Uzbekistan
  • 8. Acting Associate Professor, Tashkent State Technical University named after Islam Karimov, Uzbekistan

Description

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.

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