Low molecular weight polyethylenimine-mitochondrial leader peptide conjugate for DNA delivery to mitochondria
- Authors
- Choi, Joon Sig; Choi, Min Ji; Ko, Kyung Soo; Rhee, Byoung Doo; Pak, Youngmi Kim; Bang, In Seok; Lee, Minhyung
- Issue Date
- Sep-2006
- Publisher
- KOREAN CHEMICAL SOC
- Keywords
- gene delivery; mitochondria; leader peptide; polyethylenimine
- Citation
- BULLETIN OF THE KOREAN CHEMICAL SOCIETY, v.27, no.9, pp.1335 - 1340
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- BULLETIN OF THE KOREAN CHEMICAL SOCIETY
- Volume
- 27
- Number
- 9
- Start Page
- 1335
- End Page
- 1340
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181072
- DOI
- 10.5012/bkcs.2006.27.9.1335
- ISSN
- 0253-2964
- 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 rum. 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.
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