Electromobility of plasmid DNA in tumor tissues during electric field-mediated gene delivery.
Interstitial transport is a crucial step in plasmid DNA-based gene therapy. However, interstitial diffusion of large nucleic acids is prohibitively slow. Therefore, we proposed to facilitate interstitial transport of DNA via pulsed electric fields. To test the feasibility of this approach to gene delivery, we developed an ex vivo technique to quantify the magnitude of DNA movement due to pulsed electric fields in two tumor tissues: B16.F10 (a mouse melanoma) and 4T1 (a mouse mammary carcinoma). When the pulse duration and strength were 50 ms and 233 V/cm, respectively, we found that the average plasmid DNA movements per 10 pulses were 1.47 microm and 0.35 microm in B16.F10 and 4T1 tumors, respectively. The average plasmid DNA movements could be approximately tripled, ie to reach 3.69 microm and 1.01 microm, respectively, when the pulse strength was increased to 465 V/cm. The plasmid DNA mobility was correlated with the tumor collagen content, which was approximately eight times greater in 4T1 than in B16.F10 tumors. These data suggest that electric field can be a powerful driving force for improving interstitial transport of DNA during gene delivery.
Zaharoff
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DA
Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Durham, NC 27708, USA.
Barr
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RC
Li
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Yuan
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D000818:Animals; D003094:Collagen / Q000032:analysis; D018274:Electroporation / Q000379:methods*; D005110:Extracellular Space / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism / Q000628:therapy*; D008546:Melanoma, Experimental / Q000737:chemistry / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000493:pharmacokinetics*
D003094:Collagen