"Spinal cord injury (SCI) leads to severe physical and psychological damages. Classical pharmacotherapeutics have had limited success to treat this clinical condition and full recovery remains unachievable. With the understanding of the molecular pathology involved in neuronal injury and regeneration, new molecular targets are now under investigation. Our aim is to develop an antisense gene therapy approach mediated by single-stranded antisense oligonucleotides (ssAONs), targeted against inhibitors of axonal regeneration, in conjugation with a specific delivery platform for affected neuronal cells. The innovation of our strategy is two-fold: (1) it relies on the use and new developments of modified antisense oligonucleotides (LNA based 3rd generation ssAONs) with virtually no associated toxicity and an improved capacity to simultaneously down-regulate several genes involved in the inhibition of axonal regeneration after SCI; (2) the potential of the biodegradable and non-toxic biomaterial chitosan will be evaluated for the development of a multifunctional system capable of addressing the problem of low cellular uptake of naked oligonucleotides and especially the specific targeting of neuronal cells.The proposed ssAON strategy has immense benefits and its exploitation in the nervous system can have major implications for the treatment of several diseases in general. In conjugation with a specific delivery platform for neural cells this technology can be a major advancement in the improvement of neural regeneration after spinal cord injury."