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Expert Opin Drug Discov. 2018 Aug;13(8):709-725. doi: 10.1080/17460441.2018.1480607. Epub 2018 Jun 14.

Strategies for improving the specificity of siRNAs for enhanced therapeutic potential.

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a Cell and Molecular Biology lab, Department of Pharmaceutical Biotechnology , Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education , Manipal , Karnataka , India.
b Research Directorate of Health Sciences , Manipal Academy of Higher Education , Manipal , Karnataka , India.
c Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences , Manipal Academy of Higher Education , Manipal , Karnataka , India.


RNA interference has become a tool of choice in the development of drugs in various therapeutic areas of Post Transcriptional Gene Silencing (PTGS). The critical element in developing successful RNAi therapeutics lies in designing small interfering RNA (siRNA) using an efficient algorithm satisfying the designing criteria. Further, translation of siRNA from bench-side to bedside needs an efficient delivery system and/or chemical modification. Areas covered: This review emphasizes the importance of dicer, the criteria for efficient siRNA design, the currently available algorithms and strategies to overcome off-target effects, immune stimulatory effects and endosomal trap. Expert opinion: Specificity and stability are the primary concerns for siRNA therapeutics. The design criteria and algorithms should be chosen rationally to have a siRNA sequence that binds to the corresponding mRNA as it happens in the Watson and Crick base pairing. However, it must evade a few more hurdles (Endocytosis, Serum stability etc.) to be functional in the cytosol.


RNA interference; immune stimulatory effects and endosomal trap; siRNA; strategies to overcome off-target effects

[Indexed for MEDLINE]

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