Plasmids gene medicine

Plasmid-based gene medicine contains three components ... 

Figure 14.4 Fate of plasmid DNA after in vivo administration (modified with permission from Site-specific gene therapy design and use of plasmid-based gene medicines to control in vivo production, delivery and effect of therapeutic proteins, Eric Tomlinson (1998). In Peptide and Protein Drug Delivery, Alfred Benzon Symposium 43."...

Describe the three parts of a plasmid-based gene medicine. 

List the advantages of plasmid-based gene medicines over viral vectors. 

Nishikawa M, Takakura Y, Hashida M (2005). Pharmacokinetics of plasmid DNA-based non-viral gene medicine. Adv. Genet. 53PA 47-68. 

Bonadio, J., Smiley, E., Patil, R, and Goldstein, S. 1999a. Localized, direct plasmid gene delivery in vivo prolonged therapy results in reproducible tissue regeneration. Nature Medicine, 5,753-759. 

Murray BE, Hodel-Christian SL Bacterial resistance Theoretical and practical considerations, mutations to antibiotic resistance, characterization of R plasmid, and detection of plasmid-specific genes in Lorian V (ed) Antibiotics in Laboratory Medicine, ed 4. Baltimore, Williams Wilkins, 1996. 

The nonionic triblock copolymer polyethylene oxide-polypropylene oxide polyethylene oxide (PEO-PPO-PEO) has been widely used in medicine and has shown low toxicity. Wanka et al. [91] studied aggregation behavior of PEO-PPO-PEO polymeric micelles. In this study, the hydrophobic core of this micellar system consisted of dehydrated poly(oxy-propylene) groups which were surrounded by an outer shell of hydrated poly(oxyethylene) groups. The feasibility of using PEO-PPO PEO micelles as a topical ocular carrier for gene delivery was addressed in an in vivo study on nude mice and albino rabbits [92], Each animal eye was treated with a topical application (10 pL for mouse and 50 pL for rabbit) of 0.08 mg/mL of plasmid and 0.3% (w/v) PEO-PPO-PEO polymeric micelles. After 2 days of three times per day topical delivery, the reporter expression was detected in the treated eyes... 

In conclusion, the future for gene electrotransfer for clinical use is bright. Based on many clinical trials in human and veterinary medicine that showed positive results and safety of the approaches, especially two fields, prophylactic vaccination for infectious disease and curative vaccination combined with standard treatments for cancer will benefit in the future. Further technical developments of electrodes and generators of electric pulses on one hand and further optimization of plasmids DNA regarding the controlled expression and safety on the other hand will bring gene electrotransfer into wider use. 

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