ABSTRACT
Introduction: Small interfering RNA (siRNA) is an effective method for regulating the expression of proteins, even “undruggable” ones that are nearly impossible to target through traditional small molecule therapeutics. Delivery to the cell and then to the cytosol is the primary requirement for realization of therapeutic potential of siRNA.
Areas covered: We summarize recent advances in the design of inorganic nanoparticle with surface functionality and physicochemical properties engineered for siRNA delivery. Specifically, we discuss the main approaches developed so far to load siRNA into/onto NPs, and NP surface chemistry engineered for enhanced intracellular siRNA delivery, endosomal escape, and targeted delivery of siRNA to disease cells and tissues.
Expert Opinion: Several challenges remain in developing inorganic NPs for efficient and effective siRNA delivery. Getting the material to the chosen site is important, however the greatest hurdle may well be delivery into the cytosol, either through efficient endosomal escape or by direct cytosolic siRNA delivery. Effective delivery at the organismic and cellular level coupled with biocompatible vehicles with low immunogenic response will facilitate the clinical translation of RNAi for the treatment of genetic diseases.
Article highlights.
RNAi has the potential to revolutionize the treatment of a broad range of diseases, particularly conventionally ‘undruggable’ targets.
Several challenges exist in developing nanocarriers for effective siRNA delivery, the greatest of which are avoiding endosomal entrapment and the subsequent degradation of siRNA.
Inorganic nanoparticles provide a useful platform for the engineering of RNAi therapeutics for in vitro and in vivo applications.
The physicochemical properties of NPs determine the loading of siRNA, intracellular uptake, endosomal escape, and targeted delivery of siRNA to disease cells and tissues.
Effective delivery of siRNA at the organismic and cellular levels, coupled with the low immunogenic response of inorganic NPs, will facilitate the clinical translation of RNAi treatments for genetic diseases.
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Declaration of interest
This research was supported by NIH R01 GM077173, National Distinguished Young Scholars grant (31225009) of Chinese Natural Science Foundation, “Strategic Priority Research Program” of the Chinese Academy of Sciences, as well as t financial support from China Scholarship Council. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed