Direct injection of neuronal nitric oxide synthase into the nucleus tractus soitarii in rats and development of protein therapy

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There are some disadvantages in gene therapy. First, several days were required for protein expression after gene transfection. Second, expression of the protein cannot be controlled. On the other hand, in the protein therapy, the biological active transducted protein may have function soon. Expression of the protein can be controlled. Efficient delivery of proteins into the cells in vivo could be achieved only when the molecules are very small. It was shown that intraperitoneal injection of the β-galactosidase (β-gal) protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. This technique might be complex. There were no reports that protein transduction into the specific restricted brain area has succeeded. We demonstrated that in vivo nNOS protein direct transduction into the nucleus tractus solitarii (NTS) could change blood pressure. The in vivo delivery of biologically active proteins is a powerful therapeutic tool and the successful transduction of proteins to specific disease-bearing CNS regions would represent a remarkable clinical advance.