Proceedings of the National Academy of Sciences USA, 2011, 108 (27), 10952-10957

Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

Khuloud T. Al-Jamal, Lisa Gherardinic, Giuseppe Bardic, Antonio Nunesa, Chang Guoa, Cyrill Bussy, M. Antonia Herrero, Alberto Bianco, Maurizio Prato, Kostas Kostarelosa and Tommaso Pizzorusso

Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA delivered by functionalized carbon nanotubes reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.