Electro-gene transfer to skin using a noninvasive multielectrode array.
Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications.
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA.
Siqi
S
Guo
Amy
A
Donate
Gaurav
G
Basu
Cathryn
C
Lundberg
Loree
L
Heller
Richard
R
Heller
D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D053672:Electrochemotherapy / Q000295:instrumentation / Q000379:methods*; D004566:Electrodes; D018274:Electroporation; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006168:Guinea Pigs; D007271:Injections, Intradermal; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D049452:Green Fluorescent Proteins; D004247:DNA; D008156:Luciferases
J Clin Invest. 1996 Jun 15;97(12):2911-6
8675706
DNA Cell Biol. 2003 Dec;22(12):797-806
14683590
Curr Pharm Des. 2006;12(29):3817-25
17073680
Hum Gene Ther. 2010 Mar;21(3):357-62
19839722
Methods Mol Biol. 2008;423:249-57
18370204
Immunol Cell Biol. 2011 Mar;89(3):492-6
20838412
Genet Vaccines Ther. 2008 Dec 04;6:16
19055808
Mol Ther. 2001 Feb;3(2):249-55
11237682
Vaccine. 2003 Jan 30;21(7-8):649-58
12531334
Gene Ther. 2011 May;18(5):496-500
21179175
Gene Ther. 2010 Jul;17(7):839-45
20376097
Nat Biotechnol. 1998 Feb;16(2):168-71
9487524
Vaccine. 2010 Nov 29;28(51):8203-9
20951666
Fundam Appl Toxicol. 1990 Oct;15(3):622-30
2258024
Vaccine. 2009 Jul 9;27(32):4272-7
19450641
J Membr Biol. 2010 Jul;236(1):117-25
20652559
Biomed Eng Online. 2007 Oct 15;6:37
17937793
J Control Release. 2007 Dec 4;124(1-2):81-7
17854939
Mol Ther. 2002 Jun;5(6):668-75
12027550
Hinyokika Kiyo. 1997 Nov;43(11):823-7
9436030
Kidney Int. 2002 Jan;61(1 Suppl):S94-8
11841620
J Infect Dis. 2011 Jan 1;203(1):95-102
21148501
Gene Ther. 2010 Jun;17(6):763-9
20393507
PLoS One. 2009 Sep 30;4(9):e7226
19789652
Mol Ther. 2000 Aug;2(2):140-6
10947941
Wound Repair Regen. 2004 Jul-Aug;12(4):397-403
15260804
Mol Ther. 2009 Sep;17(9):1637-42
19532140
Gene Ther. 2005 Feb;12(4):289-98
15616607
Methods Mol Biol. 2008;423:35-59
18370189
Nat Biotechnol. 1998 Sep;16(9):867-70
9743122
Mol Ther. 2009 Apr;17(4):651-7
19240696
Vaccine. 2007 Feb 26;25(10):1814-23
17240007
J Dermatol Sci. 2007 Aug;47(2):161-4
17485200
Curr Gene Ther. 2010 Aug;10(4):312-7
20557286
FEBS Lett. 1996 Jul 8;389(3):225-8
8766704
Mol Ther. 2006 Feb;13(2):320-7
16185933
J Invest Dermatol. 2004 Oct;123(4):791-8
15373787
Gene Ther. 2010 Sep;17(9):1077-84
20410932
Eur J Dermatol. 2000 Jul-Aug;10(5):357-64
10882943
Hum Gene Ther. 2006 Sep;17(9):890-7
16972757
Curr Gene Ther. 2010 Aug;10(4):287-99
20557284
Mol Biotechnol. 2009 Oct;43(2):167-76
19562526
Br J Ind Med. 1978 Feb;35(1):1-7
629883
Adv Genet. 2005;54:83-114
16096009
J Clin Oncol. 2008 Dec 20;26(36):5896-903
19029422
Int J Pharm. 2005 Apr 27;294(1-2):53-63
15814230
Cancer Res. 1996 Mar 1;56(5):1050-5
8640760
J Vasc Res. 2000 Sep-Oct;37(5):372-80
11025400
Gene Ther. 2007 Feb;14(3):275-80
16988718
DNA Cell Biol. 2003 Dec;22(12):755-63
14683586
Neuroscience. 2001;103(4):865-72
11301197
Acta Physiol Scand. 2003 Apr;177(4):437-47
12648161
Gene Ther. 2001 Dec;8(23):1808-12
11803401
Biochem Biophys Res Commun. 1997 Apr 7;233(1):45-9
9144393
Biochim Biophys Acta. 2002 Aug 15;1572(1):1-9
12204326
Gene Ther. 2003 Apr;10(7):569-79
12646862