Abstract
Gene therapies can compensate for missing or mutated proteins, directly treat cancer, act as cancer or infectious disease vaccines, or modulate protein expression. For any type of gene therapy, the dose of expressed protein should be appropriate to correct the disease. Therapeutic development is often hampered by the concept that an optimal therapy is one with the highest and longest transgene expression coupled with the inability to predict the ultimate expression levels and duration of the therapeutic protein.
Gene therapy methods can be loosely described as biological or nonbiological. All gene therapies achieving regulatory approval to date are biological gene therapies delivered by engineered viruses. Nonbiological transfer by chemical and physical means removes the need for a biological vector and improves the safety profile. Several nonbiological delivery methods, including electroporation, have been developed to enhance gene delivery. In electroporation or electropermeabilization, controlled electric pulses produce temporary permeabilized areas in a cell’s membrane to allow molecular transfer. Electrotransfer has been used to transport a variety of molecules ranging from ions to drugs to nucleic acids across the plasma membrane and into cells.
Electrotransfer also allows molecular transfer in vivo to many tissue types. After satisfactory preclinical studies developing gene therapies using this delivery method, several therapeutic applications have reached Phase II clinical trials. This chapter overviews the steps necessary to develop a gene therapy using electrotransfer, including vector design, electric pulse choice, and electrode optimization. In addition, the complexity of the tissue target must be considered for successful development of an electrotransfer-based gene therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903
Dean DA (2013) Cell-specific targeting strategies for electroporation-mediated gene delivery in cells and animals. J Membr Biol 246:737–744. doi:10.1007/s00232-013-9534-y
Desmet CJ, Ishii KJ (2012) Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12:479–491. doi:10.1038/nri3247
Grasso RJ, Heller R, Cooley JC, Haller EM (1989) Electrofusion of individual animal cells directly to intact corneal epithelial tissue. Biochim Biophys Acta 980:9–14
Heller R, Jaroszeski M, Atkin A, Moradpour D, Gilbert R, Wands J, Nicolau C (1996) In vivo gene electroinjection and expression in rat liver. Febs Lett 389:225–228
Heller R, Cruz Y, Heller LC, Gilbert RA, Jaroszeski MJ (2010) Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode array. Hum Gene Ther 21:357–362. doi:10.1089/hum.2009.065
Jiang C, Davalos RV, Bischof JC (2015) A review of basic to clinical studies of irreversible electroporation therapy. IEEE Trans Bio-Med Eng 62:4–20. doi:10.1109/TBME.2014.2367543
Kalams SA, Parker SD, Elizaga M, Metch B, Edupuganti S, Hural J, De Rosa S, Carter DK, Rybczyk K, Frank I, Fuchs J, Koblin B, Kim DH, Joseph P, Keefer MC, Baden LR, Eldridge J, Boyer J, Sherwat A, Cardinali M, Allen M, Pensiero M, Butler C, Khan AS, Yan J, Sardesai NY, Kublin JG, Weiner DB, for the NHIVVTN (2013) Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis 208:818–829. doi:10.1093/infdis/jit236
Kreiss P, Bettan M, Crouzet J, Scherman D (1999) Erythropoietin secretion and physiological effect in mouse after intramuscular plasmid DNA electrotransfer. J Gene Med 1:245–250
Lo MM, Tsong TY, Conrad MK, Strittmatter SM, Hester LD, Snyder SH (1984) Monoclonal antibody production by receptor-mediated electrically induced cell fusion. Nature 310:792–794
Mahmood F, Gehl J (2011) Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation. Bioelectrochemistry 81:10–16. doi:10.1016/j.bioelechem.2010.12.002
Mesojednik S, Pavlin D, Sersa G, Coer A, Kranjc S, Grosel A, Tevz G, Cemazar M (2007) The effect of the histological properties of tumors on transfection efficiency of electrically assisted gene delivery to solid tumors in mice. Gene Ther 14:1261–1269
Miklavcic D, Snoj M, Zupanic A, Kos B, Cemazar M, Kropivnik M, Bracko M, Pecnik T, Gadzijev E, Sersa G (2010) Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomed Eng Online 9:10. doi:10.1186/1475-925X-9-10
Mir LM, Gehl J, Sersa G, Collins CG, Garbay JR, Billard V, Geertsen PF, Rudolf Z, O’Sullivan GC, Marty M (2006) Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator (TM) by means of invasive or non-invasive electrodes. EJC Suppl 4:14–25. doi:10.1016/j.ejcsup.2006.08.003
Mouneimne Y, Tosi PF, Gazitt Y, Nicolau C (1989) Electro-insertion of xeno-glycophorin into the red blood cell membrane. Biochem Biophys Res Commun 159:34–40
Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci U S A 90:11307–11311
Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1:841–845
Nishi T, Yoshizato K, Yamashiro S, Takeshima H, Sato K, Hamada K, Kitamura I, Yoshimura T, Saya H, Kuratsu J, Ushio Y (1996) High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. Cancer Res 56:1050–1055
Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H (1999) Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res 59:5059–5063
Okino M, Mohri H (1987) Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res 78:1319–1321
Pinyon JL, Tadros SF, Froud KE, Wong ACY, Tompson IT, Crawford EN, Ko M, Morris R, Klugmann M, Housley GD (2014) Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Sci Transl Med 6:233ra54. doi:10.1126/scitranslmed.3008177
Rizzuto G, Cappelletti M, Maione D, Savino R, Lazzaro D, Costa P, Mathiesen I, Cortese R, Ciliberto G, Laufer R, La Monica N, Fattori E (1999) Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation. Proc Natl Acad Sci U S A 96:6417–6422
Rosazza C, Deschout H, Buntz A, Braeckmans K, Rols MP, Zumbusch A (2016) Endocytosis and endosomal trafficking of DNA after gene electrotransfer in vitro. Mol Ther Nucleic Acids 5, e286. doi:10.1038/mtna.2015.59
Soden D, Larkin J, Collins C, Piggott J, Morrissey A, Norman A, Dunne C, O’Sullivan GC (2004) The development of novel flexible electrode arrays for the electrochemotherapy of solid tumour tissue. (Potential for endoscopic treatment of inaccessible cancers). Conf Proc Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Conf 5:3547–3550. doi:10.1109/IEMBS.2004.1403997
Titomirov AV, Sukharev S, Kistanova E (1991) In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim Biophys Acta 1088:131–134
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813. doi:10.1038/385810a0
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468
Zimmermann U (1982) Electric field-mediated fusion and related electrical phenomena. Biochim Biophys Acta 694:227–277
Znidar K, Bosnjak M, Cemazar M, Heller LC (2016) Cytosolic DNA sensor upregulation accompanies DNA electrotransfer in B16.F10 melanoma cells. Mol Ther Nucleic Acids 5:322. doi:10.1038/mtna.2016.34
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this entry
Cite this entry
Heller, L.C. (2017). Principles of Electroporation for Gene Therapy. In: Miklavčič, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-32886-7_48
Download citation
DOI: https://doi.org/10.1007/978-3-319-32886-7_48
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-32885-0
Online ISBN: 978-3-319-32886-7
eBook Packages: EngineeringReference Module Computer Science and Engineering