Cationic carriers of genetic material and cell death: a mitochondrial tale.
Central to gene therapy technology has been the use of cationic polymers as vectors for DNA and RNA (polyfectins). These have been presumed to be safer than viral systems which, for example, have been found to switch on oncogenes. Two key polycations that have been intensively researched for use as synthetic vectors are poly(ethylenimine) and poly(L-lysine). A frequent stumbling block with these polyfectins is that long-term gene expression in cell lines has not been achieved. Recently it has transpired that both of these polycations can induce mitochondrially mediated apoptosis. It is the aim of this review to discuss the mechanisms behind the observed polycation toxicity including roles for little studied cellular organelles in the process such as the lysosome and endoplasmic reticulum.
Hunter
A Christy
AC
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy, University of Brighton, Cockcroft Building, Lewes Road, Brighton, East Sussex BN2 4GJ, UK. c.hunter@bton.ac.uk
Moghimi
S Moein
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002412:Cations / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D011073:Polyamines / Q000633:toxicity; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000633:toxicity; D011107:Polylysine / Q000633:toxicity
D002412:Cations; D004337:Drug Carriers; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine; D011107:Polylysine