title: Cationic bolasomes with delocalized charge centers as mitochondria-specific DNA delivery systems.
abstract: Since their first discovery during the end of the 1980s, the number of diseases found to be associated with a defect in the mitochondrial genome has grown significantly. However, despite major advances in understanding mtDNA defects at the genetic and biochemical level, there is no satisfactory treatment available for the vast majority of patients. This is largely due to the fact that most of these patients have respiratory chain defects, i.e. defects that involve the final common pathway of oxidative metabolism, making it impossible to bypass the defect by giving alternative metabolic carriers of energy. These objective limitations of conventional biochemical treatment for patients with defects of mtDNA warrant the exploration of gene therapy approaches. However, mitochondrial gene therapy currently appears to be only theoretical and speculative. Any possibility for gene replacement is dependent on the use of a yet unavailable mitochondrial transfection vector. In this review we describe the current state of the development of mitochondrial DNA delivery systems. We also summarize our own efforts in exploring the properties of dequalinium, a cationic bolaamphiphile with delocalized charge centers, for the design of a vector suited for the transport of DNA to mitochondria in living cells.
authors.affiliation: Northeastern University, Bouve College of Health Sciences, Department of Pharmaceutical Sciences, 360 Huntington Avenue, Boston, MA 02115, USA. vweissig@hotmail.com
authors.forename: V
authors.initials: V
authors.lastname: Weissig
authors.forename: V P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000737:chemistry; D002412:Cations / Q000008:administration & dosage; D004272:DNA, Mitochondrial / Q000008:administration & dosage*; D003868:Dequalinium / Q000008:administration & dosage* / Q000737:chemistry; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008081:Liposomes; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017240:Mitochondrial Myopathies / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000891:Anti-Infective Agents, Local; D002412:Cations; D004272:DNA, Mitochondrial; D008081:Liposomes; D008563:Membrane Lipids; D003868:Dequalinium