DNA electrotransfer: its principles and an updated review of its therapeutic applications

André, Franck; Mir, Lluis M.

doi:10.1038/sj.gt.3302367

Cited by 262 publications

(175 citation statements)

References 138 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…The electroporation method has been widely used to deliver plasmid DNA in vivo into a variety of organs/ tissues, [55][56][57][58] as well as solid tumors including melanoma. 55,56,[59][60][61] Electroporation was applied to RNAi by Pekarik et al 62 who transfected synthetic siRNA in ovo into chick embryos, while we first documented electrotransfer of siRNA into a mammalian organ in vivo.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

et al. 2006

View full text Add to dashboard Cite

Microphthalmia-associated transcription factor (Mitf) is critically involved in melanin synthesis as well as differentiation of cells of the melanocytic lineage. Some earlier studies suggested that Mitf is also essential in the survival of melanoma cells, but this notion remains controversial. We synthesized short interfering RNA (siRNA) duplexes corresponding to the mitf sequence and transfected them into B16 melanoma. Lipid-mediated transfection in vitro of Mitfspecific siRNA resulted in specific downregulation of Mitf and of the tyrosinase that is a transcriptional target of Mitf. This treatment also remarkably reduced the viability of melanoma cells by inducing apoptosis. To examine the potential feasibility of RNAi therapy against melanoma, B16 cells were subcutaneously injected into syngenic mice and siRNA was transfected into the pre-established tumor by means of electroporation. The Mitf-specific siRNA drastically reduced outgrowth of subcutaneous melanoma, while nonspecific siRNA failed to affect tumor progression. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-based analysis of tumor specimens demonstrated that the tumor cells transfected with Mitf-siRNA effectively underwent apoptosis in vivo. The present results indicate that Mitf plays important roles in melanoma survival. Intratumor electrotransfer of Mitf-specific siRNA may provide a powerful strategy for therapeutic intervention of malignant melanoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

et al. 2006

View full text Add to dashboard Cite

show abstract

“…By applying an electric field to tissues that have received DNA plasmids coding for specific proteins, the expression of the proteins has been increased significantly compared to that expressed in the absence of electroporation. 1 These findings suggest that this method could be utilized for the effective delivery of genes expressing 'therapeutic' proteins, including cytokines, with the potential of enhancing a clinical effect.…”

Section: Introductionmentioning

confidence: 99%

Regression of subcutaneous B16 melanoma tumors after intratumoral delivery of an IL-15-expressing plasmid followed by in vivo electroporation

et al. 2006

View full text Add to dashboard Cite

In vivo electroporation has been used to efficiently deliver drugs and 'therapeutic' genes to tumors, including melanoma lesions. This study reports on the effect of intratumoral delivery of an optimized DNA plasmid expressing interleukin-15 (pIL-15) on established murine melanoma tumors. IL-15 has been demonstrated to have a pivotal role in the function of memory CD8 þ T cells and natural killer cells, which are critical for tumor immunosurveillance. In this study, C57BL/6 mice were injected with B16.F10 melanoma cells and randomized into different experimental groups: untreated (PÀVÀEÀ), treated with pIL-15 (P þ ) or backbone plasmid (V þ ), with or without electroporation (E þ or EÀ). Treatment was performed intratumorally with 50 mg of plasmid on days 0, 4 and 7 and tumor volume/size, tumor regression and long-term survival were measured. At day 100 after initiation of treatment, the percentage of mice surviving with complete tumor regression in the PÀV þ E þ , P þ VÀEÀ, P þ VÀE þ and PÀVÀEÀ treatment groups were 0, 12.5, 37.5 and 0%, respectively. These results demonstrate the ability of pIL-15 to mediate B16 melanoma regression, with the effect being significantly enhanced by electroporative delivery. This is the first description of the ability of a naked DNA plasmid expressing IL-15 to alone mediate complete regression of B16 melanoma tumors and underscores the potential clinical use of these plasmids for the treatment of malignant tumors when delivered with in vivo electroporation.

show abstract

“…These data agree with expression optimization studies performed in other tissues. [17][18][19][20] A model based on previously collected data 21 analyzes viability (V) as well as number of molecules taken up (N) after electroporation delivery. For multiple pulses, the model predicts that at field strengths of o1000 V/cm, the NV increases as pulse length increases.…”

Section: Cutaneous Gene Transfer With Electroporationmentioning

confidence: 99%

Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode

et al. 2006

View full text Add to dashboard Cite

DNA electrotransfer: its principles and an updated review of its therapeutic applications

Cited by 262 publications

References 138 publications

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

Regression of subcutaneous B16 melanoma tumors after intratumoral delivery of an IL-15-expressing plasmid followed by in vivo electroporation

Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode

Contact Info

Product

Resources

About