Title:Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus
Volume: 24
Issue: 1
Author(s): Sayed Sartaj Sohrab*, Sherif Aly El-Kafrawy, Zeenat Mirza, Mohammad Amjad Kamal and Esam Ibraheem Azhar
Affiliation:
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah,Saudi Arabia
Keywords:
MERS-CoV, RNA interference, siRNA, designing, delivery, nanoparticles.
Abstract: Background: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April
2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi
approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by
RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published.
Methods: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential
siRNA can be designed to silence a desired gene by considering many factors like target site, specificity,
length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses.
The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and
quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral
gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles,
inorganic nanoparticles and polymeric nanoparticles.
Conclusion: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but
also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative
technology has attracted researchers, academia and pharmaceuticals industries towards designing and development
of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs
can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against
MERS-CoV.
