Document Type
Article
Publication Date
10-7-2020
Abstract
The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.
Recommended Citation
Sajid MI, Moazzam M, Kato S, Yeseom Cho K, Tiwari RK. Overcoming barriers for siRNA therapeutics: From bench to bedside. Pharmaceuticals. 2020; 13(10):294. https://doi.org/10.3390/ph13100294
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Cell Anatomy Commons, Cell Biology Commons, Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medicinal and Pharmaceutical Chemistry Commons, Other Cell and Developmental Biology Commons, Other Pharmacy and Pharmaceutical Sciences Commons
Comments
This article was originally published in Pharmaceuticals, volume 13, issue 10, in 2020. https://doi.org/10.3390/ph13100294