PT - JOURNAL ARTICLE AU - So Yeon Pakr AU - Won Woo Lee TI - Dicer substrate siRNA-mediated silencing of human sodium iodide symporter (hNIS) gene in hNIS-expressing cell lines DP - 2009 May 01 TA - Journal of Nuclear Medicine PG - 1591--1591 VI - 50 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/50/supplement_2/1591.short 4100 - http://jnm.snmjournals.org/content/50/supplement_2/1591.full SO - J Nucl Med2009 May 01; 50 AB - 1591 Objectives We designed a human sodium iodide symporter (hNIS)-targeted dicer substrate small interfering RNA (dsiRNA) and evaluated the silencing effects of the dsiRNA in stably hNIS-expressing cell lines. Methods Three stably hNIS-expressing cell lines (2 cancer cell lines, C6-hNIS and CT26-hNIS; 1 stem cell line, rMSC-hNIS) were transfected using the dsiRNA and lipofectamine 2000. 48 hours after the transfection, I-125 uptake tests were performed. The dsiRNA-mediated silencing effects (0.001, 0.01, 0.1, 1, and 30 nM) were compared to the effects of specific hNIS inhibitor, NaClO4 (300 µM). Results C6-hNIS cells revealed the I-125 uptake of 539.9±16.9 picomole/106 cells, whereas NaClO4 inhibited C6-hNIS cells showed 113.9±19.6 picomole/106 cells. The dsiRNA transfection (30 nM) to C6-hNIS cells completely inhibited I-125 uptake as 74.5±18.9 picomole/106 cells. CT26-hNIS cells showed the I-125 uptake of 1658.6±50.8 picomole/106 cells, whereas NaClO4 inhibited CT26-hNIS cells showed 53.3±10.7 picomole/106 cells. The 1 nM concentration of dsiRNA to CT26-hNIS cells inhibited 81% of I-125 uptake. rMSC-hNIS cells had the I-125 uptake of 394.6±48.1 picomole/106 cells, whereas NaClO4 inhibited rMSC-hNIS cells had 152.8±15.1 picomole/106 cells. The dsiRNA transfection (30 nM) to rMSC-hNIS cells completely inhibited I-125 uptake as 143.5±29.0 picomole/106 cells. Conclusions The hNIS-targeted dsiRNA potently silenced the hNIS function in stably hNIS-expressing cells. The potency of hNIS inhibition using the dicer substrate siRNA was comparable to that of hNIS-inhibitor (NaClO4) treatment. The development of effective delivery systems for dsiRNA in vivo may be possible using the hNIS-targeted dsiRNA.