Reversible treatments (deterioration or improvement) of pressure overload‐induced left ventricular hypertrophy and heart failure are readily achieved via one functional polyaminoglycoside vector (SS‐HPT) loaded with Drd5 siRNA (SS‐HPT/Drd5 siRNA) or Drd5 plasmid (SS‐HPT/Drd5 plasmid). Here, DRD5 is linked to heart failure.