Ahmed Abosalha

By Ahmed Kh. Abosalha, Stephanie Makhlouf, Paromita Islam, Shyam Mohapatra and Satya Prakash

RNA interference (RNAi), a mechanism for post-transcriptional gene silencing using small interfering RNA (siRNA) or microRNA (miRNA), has emerged as a promising approach for managing numerous genetic disorders by selectively targeting and degrading the mRNA of implicated genes. However, the clinical application of these therapeutics is hindered by significant challenges that limit their delivery to target sites. RNAi therapeutics face multiple extracellular and intracellular barriers post-administration, including rapid glomerular excretion, recognition, and opsonization by the reticuloendothelial system (RES), and catalytic degradation by nucleases, leading to poor cellular and tissue penetration. To address these challenges, various delivery strategies have been explored to efficiently transport these RNAi therapeutics to their intended tissues. These strategies encompass chemical modification, bioconjugation with specific ligands, and carrier-mediated approaches. Nanotechnology-based delivery systems have demonstrated remarkable capabilities in encapsulating and delivering these molecules to their specific cells. Therefore, there is an urgent need to develop innovative delivery systems that can effectively encapsulate and target RNAi therapeutics. By targeting key genes, RNA interference holds the potential to address numerous genetic, viral, and cancer diseases at an early stage. This book chapter explores several studies detailing diverse design strategies aimed at overcoming the hurdles encountered in RNAi delivery.

Part of the book: Beyond the Blueprint - Decoding the Elegance of Gene Expression [Working title]