Addressing Cognitive Impairment by Silencing a Novel Target That Acts As the “Break on Memory”

Cognition - proof of concept

  • Noninvasive IV injection of nanoparticles of the trojan-horse complexed electrostatically to an antisense RNA (siRNA)
  • Very low effective dose
  • Rapid brain uptake after IV injection (Figure 3)
  • Massive memory enhancement (6.8x) in wild-type mice (Figure 4A)
  • Massively reduces expression (80% knockdown) of the targeted gene mRNA (Figure 4B)
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Figure  3. Rapid Brain Uptake of OCCT:lynx1 siRNA in vivo. Uptake of the labeled siRNA complexed to OCCT was observed after few minute (A,B)  and 1 hour (B1). No signal was observed when only labeled siRNA was injected (C, C1).

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Figure 4. OCCT-lynx1 siRNA improves memory. Increased novel object recognition memory (A) and knockdown of the target gene (B) was observed in OCCT-lynx1 siRNA treated mice