Gene Knockdown in the Olfactory Bulb, Amygdala, and Hypothalamus by Intranasal siRNA Administration

• 발행기관: 대한해부학회
• 저자명: Il-Doo Kim Seung-Woo Kim Ja-Kyeong Lee
• 간행물 정보: 『대한해부학회지』제42권 제4호, 285~292쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2009.12.31

영문 초록

Intranasal administration provides a method of bypassing the blood brain barrier, which separates the systemic circulating system and central interstitial fluid, and directly drugs to the central nervous system. This method also circumvents first-pass elimination by the liver and gastrointestinal tract. In the present study, the authors investigated intranasal siRNA delivery efficiency by using FITC-labeled transfection control siRNA and a genespecific siRNA. The localization of fluorescence-tagged siRNA revealed that siRNA was delivered to cells in the olfactory bulb and that the level of the siRNA target gene(alpha B-crystallin) was significantly reduced in the same area. siRNA was delivered to processes as well as nuclei and cytoplasm. At 12 hrs after intranasal delivery, siRNA-mediated target gene reduction was observed in other more distally located brain regions, for example, in the amygdala, entorhinal cortex, and hypothalamus. Target gene knockdown was demonstrated by double immunohistochemistry, which demonstrated target gene suppression was detected not only in neurons but in glia, for example, astrocytes. These results indicate that intranasal siRNA delivery offers an efficient means of reducing specific target genes in certain regions of the brain and of performing gene knockdown-mediated therapy.

키워드

siRNA Intranasal delivery Olfactory bulb ∝b-crystallin Gene knockdown