caa a22 4500 445314354 CHVBK 20180317142641.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0546-y doi (NATIONALLICENCE)springer-10.1007/s11095-011-0546-y Transduction of Human Recombinant Proteins into Mitochondria as a Protein Therapeutic Approach for Mitochondrial Disorders [Elektronische Daten] [Lefkothea Papadopoulou, Asterios Tsiftsoglou] ABSTRACT: Protein therapy is considered an alternative approach to gene therapy for treatment of genetic-metabolic disorders. Human protein therapeutics (PTs), developed via recombinant DNA technology and used for the treatment of these illnesses, act upon membrane-bound receptors to achieve their pharmacological response. On the contrary, proteins that normally act inside the cells cannot be developed as PTs in the conventional way, since they are not able to "cross” the plasma membrane. Furthermore, in mitochondrial disorders, attributed either to depleted or malfunctioned mitochondrial proteins, PTs should also have to reach the subcellular mitochondria to exert their therapeutic potential. Nowadays, there is no effective therapy for mitochondrial disorders. The development of PTs, however, via the Protein Transduction Domain (PTD) technology offered new opportunities for the deliberate delivery of human recombinant proteins inside eukaryotic subcellular organelles. To this end, mitochondrial disorders could be clinically encountered with the delivery of human mitochondrial proteins (engineered via recombinant DNA and PTD technologies) at specific intramitochondrial sites to exert their function. Overall, PTD-mediated Protein Replacement Therapy emerges as a suitable model system for the therapeutic approach for mitochondrial disorders. Springer Science+Business Media, LLC, 2011 mitochondrial disorders nationallicence protein therapy nationallicence protein transduction nationallicence PTDs nationallicence aa : amino acids nationallicence CDS : coding sequence nationallicence CNS : central nervous system nationallicence COX : Cytochrome c Oxidase nationallicence E. coli : Escherichia coli nationallicence ERT : Enzyme Replacement Therapy nationallicence FDA : Food and Drug Administration nationallicence GFP : Green Fluorescent Protein nationallicence GMOs : genetically modified organisms nationallicence IBs : inclusion bodies nationallicence IMS : intermembrane space nationallicence IPTG : isopropyl-beta-D-thiogalactopyranoside nationallicence L : N-terminal Leader Peptide nationallicence LAD : Lipoamide Dehydrogenase nationallicence mab : monoclonal antibody nationallicence MPP : Mitochondrial Processing Peptidase nationallicence mtDNA : mitochondrial DNA nationallicence MTS : Mitochondrial Targeting Signal Peptide nationallicence ΝABs : Neutralizing Antibodies nationallicence nDNA : muclear DNA nationallicence OXPHOS : Oxidative Phosphorylation System nationallicence PDHC : Pyruvate Dehydrogenase Complex nationallicence PEG : poly(ethylene glycol) nationallicence PRT : Protein Replacement Therapy nationallicence PTD : Protein Transduction Domain nationallicence PTs : Protein Therapeutics nationallicence ROS : Reactive Oxygen Species nationallicence TAT : a Protein Transduction Domain nationallicence TCA : Tricarboxylic acid cycle nationallicence TFAM : Mitochondrial Transcription Factor A nationallicence Papadopoulou Lefkothea Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki (A.U.TH.), GR54124, Thessaloniki, Macedonia, Greece aut Tsiftsoglou Asterios Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki (A.U.TH.), GR54124, Thessaloniki, Macedonia, Greece aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2639-2656 0724-8741 28:11<2639 2011 28 11095 https://doi.org/10.1007/s11095-011-0546-y text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0546-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Papadopoulou Lefkothea Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki (A.U.TH.), GR54124, Thessaloniki, Macedonia, Greece aut NATIONALLICENCE 700 1- Tsiftsoglou Asterios Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki (A.U.TH.), GR54124, Thessaloniki, Macedonia, Greece aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2639-2656 0724-8741 28:11<2639 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer