Antisense oligonucleotide therapy for neurodegenerative disease
J. Clin. Invest. Richard A. Smith, et al. 116:2290 doi:10.1172/JCI25424 [Go to this article.]

Figure 1
Distribution of antisense oligonucleotides after infusion into the right lateral ventricle in rats and Rhesus monkeys. (A and B) Antisense oligonucleotides were continuously infused for 2 weeks via infusion pump into the right lateral ventricle of normal rats at 100 μg/d (A) or Rhesus monkeys at 1 mg/d (B). Tissues were collected, and extracts were analyzed for oligonucleotide content by capillary gel electrophoresis. Mean ± SD are shown (n = 6 [A]; 2 [B]). (C–M) A 24-mer modified oligonucleotide, Isis¹³⁹²⁰, was infused for 2 weeks into the right lateral ventricle at 100 μg/d in rats (C–E) or 1 mg/d in Rhesus monkeys (F–M). After perfusion, distribution of the oligonucleotide was determined by immunohistochemistry using a monoclonal antibody that recognizes the oligonucleotide (C–E, F, H, and J–M) or astrocytes (GFAP; G and I). No oligonucleotide staining was seen in animals infused with saline only (D and H), nor in an animal infused with oligonucleotide but using secondary antibody only (E). Scale bars: 50 μm.