Mitochondriotropic Cationic Vesicles A Strategy Towards Mitochondrial Gene Therapy

Authors: Weissig V.; Torchilin V.P.

Source: Current Pharmaceutical Biotechnology, Volume 1, Number 4, December 2000 , pp. 325-346(22)

Publisher: Bentham Science Publishers

Abstract:

The number of diseases found to be associated with defects of the mitochondrial genome has grown significantly over the last decade. Despite major advances in understanding mtDNA defects at the genetic and biochemical level, there is no satisfactory treatment for the vast majority of patients available. This is largely due to the fact that almost all mitochondrial DNA defects involve the final common pathway of oxidative metabolism making it impossible to bypass the defect by giving alternative metabolic carriers of energy. These seemingly objective limitations of conventional biochemical treatment for patients with defects of mtDNA warrant the exploration of gene therapeutic approaches. However, mitochondrial gene therapy still appears only theoretical and speculative. Any possibility for gene replacement is dependent on the use of a yet unavailable mitochondria-specific transfection vector.

Based upon an analysis of the self-assembly behavior of dequalinium, a cationic single-chain bolaamphiphile which is known to selectively accumulate in mitochondria, we have developed a whole new strategy for mitochondria-specific DNA delivery. We have succeeded in preparing vesicles made of dequalinium, which we termed DQAsomes (U.S. Patent 6,090,619). We have shown that DQAsomes efficiently bind and protect DNA and we could demonstrate that DQAsome DNA complexes selectively release DNA at cardiolipin-rich liposomes mimicking both, the inner and the outer mitochondrial membrane. Based on the intrinsic property of dequalinium to preferentially accumulate in mitochondria in response to the electrochemical gradient at the mitochondrial membrane and based on the selective DNA release at mitochondria-like membranes we propose DQAsomes as the first mitochondria-specific vector to deliver DNA to mitochondria in living cells.

Keywords: Mitochondriotropic cationic vesicles; Dequalinium; DQAsomes; Mitochondrial DNA; Transfection

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201003378870

Publication date: 2000-12-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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• In this Subject: Nutrition & Food ,  Biotechnology ,  Pharmacology
• By this author: Weissig V. ;  Torchilin V.P.

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