Hashimoto Research Unit, RIKEN BSI, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
J Neurosci Methods. 2011 Jan 15;194(2):316-20. doi: 10.1016/j.jneumeth.2010.10.027. Epub 2010 Nov 11.
Adenoviral (Ad) vectors are useful for in vivo gene transfer into the brain. If Ad vectors are injected into the ventricle of mouse embryonic brain, Ad vectors introduce a foreign gene into neural progenitor cells on the surface of ventricle. However, Ad vectors were unable to deliver a foreign gene to a targeted region of the embryonic brain because Ad vectors evenly infected the neural progenitor cells on the surface of ventricle. Therefore, the Ad infection to the neural progenitor cells was uncontrollable. To develop a directional gene-transfer with Ad vector, we generated Ad vector tagged with magnetic nanoparticles (Ad-mag) by linking a biotinylated adenovirus vector with a streptavidin-conjugated magnetic nanoparticle. Ad-mags were attracted by magnetic force in vitro and in vivo. When Ad-mags were injected into the ventricle of mouse embryo and a strong magnet was attached to the head of the embryo, Ad-mags were attracted to the restricted direction or region where the magnet was placed. As a result, Ad-mags efficiently introduced a foreign gene into the restricted region of the brain.
腺病毒（Ad）载体可用于将基因活体转入大脑。如果将 Ad 载体注入鼠胚胎大脑的脑室中，Ad 载体可将外源基因导入脑室表面的神经祖细胞。然而，由于 Ad 载体可均匀感染脑室表面的神经祖细胞，因此无法将外源基因递送至胚胎大脑的靶向区域。为了实现用 Ad 载体进行定向基因转移，我们通过将生物素化腺病毒载体与链霉亲和素偶联的磁性纳米颗粒连接，生成了标记有磁性纳米颗粒的 Ad 载体（Ad-mag）。Ad-mag 在体外和体内均会受到磁力吸引。当 Ad-mag 被注入鼠胚胎的脑室中，且在胚胎头部附上一块强磁铁时，Ad-mag 会被吸引至放置磁铁的受限方向或区域。结果，Ad-mag 可将外源基因高效地导入大脑的受限区域。
