Strategies for improving the specificity of siRNAs for enhanced therapeutic potential

Aditya Kiran Gatta, Raghu Chandrashekhar Hariharapura, Nayanabhirama Udupa, Meka Sreenivasa Reddy, Venkata Rao Josyula

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


Introduction: 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.

Original languageEnglish
Pages (from-to)709-725
Number of pages17
JournalExpert Opinion on Drug Discovery
Issue number8
Publication statusPublished - 03-08-2018

All Science Journal Classification (ASJC) codes

  • Drug Discovery


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