Brain Targeting of siRNA via Intranasal Pathway

Brain diseases are the most serious health problems; represent a significant and worldwide public health problem. Small interfering RNAs (siRNAs) can initiate specific silencing of genes and are potential therapeutic agents for many genetically influenced diseases including brain disease. However, on systemic administration the blood-brain barrier (BBB) poses most significant obstacle for the therapeutic siRNAs delivery to the brain. Therefore, the development of successful approaches to enhance siRNA delivery to the brain is of immense interest in clinical and pharmaceutical research. At present, intranasal delivery approach serves as an effective mode of direct delivery of siRNAs to brain by bypassing BBB. In this review, we describe the principles of RNA interference (RNAi) machinery; challenges associated with siRNAs in therapeutics brain targeting and summarize the recent progress made in the use of vector based siRNA technology. Further, it is anticipated that intranasal delivery approach will have a very important role to play in the future for the translation of siRNAs therapeutics from bench to bedside for different brain diseases.