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http://dx.doi.org/10.5012/bkcs.2006.27.9.1335

Low Molecular Weight Polyethylenimine-Mitochondrial Leader Peptide Conjugate for DNA Delivery to Mitochondria  

Choi, Joon-Sig (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Choi, Min-Ji (Department of Bioengineering, College of Engineering, Hanyang University)
Go, Gyeong-Su (Department of Internal Medicine, Mitochondrial Research Group, College of Medicine, Inje University)
Rhee, Byoung-Doo (Department of Internal Medicine, Mitochondrial Research Group, College of Medicine, Inje University)
KimPak, Young-Mi (Asan Institute for Life Science, University of Ulsan)
Bang, In-Seok (MyGene Bioscience Institute)
Lee, Min-Hyung (Department of Bioengineering, College of Engineering, Hanyang University)
Publication Information
Bulletin of the Korean Chemical Society / v.27, no.9, 2006 , pp. 1335-1340 More about this Journal
Abstract
It has been found that a number of diseases are associated with mutations in the mitochondrial DNA. Therapeutic gene delivery to mitochondria has been suggested as a clinical option for these diseases. In this study, we developed a gene carrier to mitochondria by the conjugation of mitochondrial leader peptide (LP) to polyethylenimine (PEI). Mitochondrial LP conjugated PEI (PEI-LP) was synthesized with low molecular weight PEI (2,000 Da, PEI2K). Gel retardation assay showed that PEI2K-LP formed complexes at a 1.0/1 weight ratio. In addition, PEI2K-LP protected DNA from the enzymatic degradation for at least 60 min, while naked DNA was completely degraded within 20 min. PEI2K-LP was compared with LP conjugated high molecular weight PEI (25,000 Da, PEI25K) in terms of toxicity and delivery efficiency. MTT assay showed that PEI2K-LP had much lower cytotoxicity than PEI25K-LP to 293 cells. In addition, cell-free DNA delivery assay showed that PEI2K-LP delivered more DNA to mitochondria at a 1.8/1 weight ratio than naked DNA or PEI. This result suggests that PEI2K-LP may be useful for the development of mitochondrial gene therapy system with lower cytotoxicity.
Keywords
Gene delivery; Mitochondria; Leader peptide; Polyethylenimine;
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