Gene suppression with chitosan nanoparticles

Abstract

The first tool in gene therapy is DNA internalization for genetic deficiencies, and another tool is used to suppress the biosynthesis of protein by the introduction of antisense oligonucleotides (ASOs) or small interfering ribonucleic acid (siRNAs). ASOs and siRNAs represent an exciting new area for the pharmaceutical industry. These molecules can knock down the expression of target genes through the use of RNA interference (RNAi) pathway. For the development of ASOs and siRNAs, as therapeutics agents, two key problems must be addressed: serum stability and delivery efficiency/specificity. Further, a suitable delivery system is required. Chitosan nanoparticles are attractive gene delivery systems because they are biodegradable and biocompatible and have low toxicity and immunogenicity. Conventional nanoparticle preparation techniques are used for their production. Chitosan and modified forms of chitosan can be used to prepare nanoparticles. Nanoparticle-based therapeutics can be administered by different routes, such as pulmonary, nasal, dermal, and parenteral. ASO and siRNA technologies have many similarities, such as gene inhibition and others. However, there are also some differences between these technologies; ASO accumulate in the nucleus of the cell and therefore can be used to alter splicing of mRNA, while siRNAs are known to function in the cytoplasm. © Springer-Verlag Berlin Heidelberg 2016.