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 4
Antisense oligonucleotides complementary to humanSOD1 mRNA decrease SOD1 protein levels in SOD1^G93A rat liver and spinal cord. (A) An oligonucleotide active against human SOD1 mRNA as well as a rat mRNA–specific oligonucleotide (SOD^r146192) was injected intraperitoneally 3 times per week (37.5 mg/kg at a concentration of 3 M) into adult rats expressing a low copy number human SOD1^G93A transgene (line L26L; ref. 27). After 3 weeks, liver extracts were prepared and analyzed by immunoblotting using an antibody that recognizes rat and human SOD1 with equal affinity (18). (B–D) Antisense oligonucleotides complementary to human SOD1 mRNA were infused into the right lateral ventricle of 65-day-old SOD1^G93A rats at 100 μg/d for 28 days. (B) RNA was prepared from tissue extracts, and SOD1 RNA levels were measured by real-time RT-PCR. (C and D) Protein levels for SOD1 and α-tubulin were analyzed in parallel extracts by immunoblotting with an antibody recognizing human and rat SOD1 with equal affinity (C) and were quantified for cervical cord (D). *P < 0.05 versus SOD^scrambled; Student’s t test. Mean ± SD are shown (n = 4 [SOD^scrambled]; 8 [SOD^r/h333611]).