siRNA delivery for treatment of degenerative diseases, new hopes and challenges

Abstract Degenerative diseases are marked by continuous and progressive deterioration of the function of cells which is not caused by any underlying trauma or infection. The economic and social burdens of degenerative diseases on societies are rapidly increasing especially since the global population is ageing. There is no satisfactory treatment for degenerative diseases since they are characterized by cell ageing. Available therapeutics only alleviate the symptoms of the patients and do not halt the progression of the disease. siRNA therapeutics in the recent years have gained much interest because they can regulate gene expression, modify epigenetic changes and halt diseases at post-translational level. Some siRNA formulations that silence signal mediators responsible for cell degeneration have entered clinical trial. However, problems in siRNA delivery, its duration of action and off-target effects have hindered the clinical application of therapeutic siRNAs. In this article, siRNA therapy for a plethora of degenerative diseases, their potentials and limitations and mechanism of action and their delivery are comprehensively reviewed. These include neurodegenerative, musculoskeletal, heart, lung, liver, skin and ocular degenerative diseases. Results of studies revealed high efficiency and specificity for siRNA therapy that is able to overcome some limitations of conventional chemical therapeutics.