The rapid progress achieved in the development of many
biopharmaceuticals had a tremendous impact on the
therapy of many metabolic/
genetic disorders. This type of fruitful approach, called
protein replacement
therapy (PRT), aimed to either replace the deficient or malfunctional
protein in human tissues that act either in plasma membrane or via a specific
cell surface receptor. However, there are also many metabolic/
genetic disorders attributed to either deficient or malfunctional
proteins acting intracellularly. The recent developments of
Protein Transduction Domain (PTD) technology offer new opportunities by allowing the intracellular delivery of
recombinant proteins of a given therapeutic interest into different subcellular sites and organelles, such as mitochondria and other entities. Towards this pathway, we applied successfully PTD Technology as a
protein therapeutic approach, in vitro, in SCO2 deficient primary fibroblasts, derived from patient with mutations in human SCO2 gene, responsible for fatal, infantile cardioencephalomyopathy and
cytochrome c oxidase deficiency. In this work, we radiolabeled the recombinant TAT-L-Sco2 fusion
protein with technetium-99 m to assess its in vivo biodistribution and fate, by increasing the sensitivity of detection of even low levels of the transduced
recombinant protein. The biodistribution pattern of [99mTc]Tc-TAT-L-Sco2 in mice demonstrated fast blood clearance, significant hepatobiliary and renal clearance. In addition, western blot analysis detected the recombinant TAT-L-Sco2
protein in the isolated mitochondria of several mouse tissues, including heart, muscle and brain. These results pave the way to further consider this PTD-mediated
Protein Therapy Approach as a potentially alternative treatment of genetic/metabolic disorders.