Cationic bolasomes with delocalized charge centers as mitochondria-specific DNA delivery systems

Since their first discovery during the end of the 1980s, the number of dise ases found to be associated with a defect in the mitochondrial genome has g rown significantly. However, despite major advances in understanding mtDNA defects at the genetic and biochemical level, there is no satisfactory trea tment available for the vast majority of patients. This is largely due to t he fact that most of these patients have respiratory chain defects, i.e. de fects that involve the final common pathway of oxidative metabolism, making it impossible to bypass the defect by giving alternative metabolic carrier s of energy. These objective limitations of conventional biochemical treatm ent for patients with defects of mtDNA warrant the exploration of gene ther apy 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 mitoch ondrial DNA delivery systems. We also summarize our own efforts in explorin g 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. (C) 2001 Elsevier Science BN. All rights reserved.