Duration and level of transgene expression after gene electrotransfer to skin in mice

TY - JOUR

T1 - Duration and level of transgene expression after gene electrotransfer to skin in mice

AU - Gothelf, A

AU - Eriksen, Jens Ole

AU - Hojman, P

AU - Gehl, Julie

PY - 2010/7/1

Y1 - 2010/7/1

N2 - In development of novel vaccines, attention is drawn to DNA vaccinations. They are heat stable and can be easily produced. Gene electrotransfer is a simple and nonviral means of transferring DNA to cells and tissues and is attracting increasing interest. One very interesting perspective with gene electrotransfer is that choice of tissue can determine the duration of transgene expression. With gene electrotransfer to muscle, long-term expression, that is beyond 1 year, can be obtained, whereas gene electrotransfer to skin gives short-term expression, which is desirable in, for example, DNA vaccinations. Level and duration of transgene expression after gene electrotransfer to skin is essential and here we present data from two independent quantitative studies. Using in vivo bioimaging of a far-red fluorescent molecule, Katushka, allowing for continuous monitoring of local gene expression, compared with measurements of a systemic transgene, that is, serum erythropoietin (EPO) after gene electrotransfer with EPO to skin, we found a significant increase in transgene expression (P<0.01) with a peak 9 days (Katushka) and 14 days (EPO) after transfection. Duration of expression could be 3-4 weeks, which is a suitable time frame for vaccinations and is applicable, for example, in gene therapy for wound healing or treatment of cancer.

AB - In development of novel vaccines, attention is drawn to DNA vaccinations. They are heat stable and can be easily produced. Gene electrotransfer is a simple and nonviral means of transferring DNA to cells and tissues and is attracting increasing interest. One very interesting perspective with gene electrotransfer is that choice of tissue can determine the duration of transgene expression. With gene electrotransfer to muscle, long-term expression, that is beyond 1 year, can be obtained, whereas gene electrotransfer to skin gives short-term expression, which is desirable in, for example, DNA vaccinations. Level and duration of transgene expression after gene electrotransfer to skin is essential and here we present data from two independent quantitative studies. Using in vivo bioimaging of a far-red fluorescent molecule, Katushka, allowing for continuous monitoring of local gene expression, compared with measurements of a systemic transgene, that is, serum erythropoietin (EPO) after gene electrotransfer with EPO to skin, we found a significant increase in transgene expression (P<0.01) with a peak 9 days (Katushka) and 14 days (EPO) after transfection. Duration of expression could be 3-4 weeks, which is a suitable time frame for vaccinations and is applicable, for example, in gene therapy for wound healing or treatment of cancer.

U2 - 10.1038/gt.2010.35

DO - 10.1038/gt.2010.35

M3 - Journal article

SN - 0969-7128

VL - 17

SP - 839

EP - 845

JO - Gene Therapy (Basingstoke)

JF - Gene Therapy (Basingstoke)

IS - 7

ER -