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Preclinical development of siRNA therapeutics: towards the match between fundamental science and engineered systems.

Author information

Affiliations

  • 1. iMed.UL - Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal.
      Authors
    • Videira M 1
    • Arranja A 1
    • Rafael D 1
    • Gaspar R 1
    (4 authors)

ORCIDs linked to this article

Nanomedicine : Nanotechnology, Biology, and Medicine, 10 Dec 2013, 10(4):689-702
https://doi.org/10.1016/j.nano.2013.11.018 PMID: 24333589 

Review

Abstract 

The evolution of synthetic RNAi faces the paradox of interfering with the human biological environment. Due to the fact that all cell physiological processes can be target candidates, silencing a precise biological pathway could be challenging if target selectivity is not properly addressed. Molecular biology has provided scientific tools to suppress some of the most critical issues in gene therapy, while setting the standards for siRNA clinical application. However, the protein down-regulation through the mRNA silencing is intimately related to the sequence-specific siRNA ability to interact accurately with the potential target. Moreover, its in vivo biological fate is highly dependent on the successful design of a vehicle able to overcome both extracellular and intracellular barriers. Anticipating a great deal of innovation, crucial to meet the challenges involved in the RNAi therapeutics, the present review intends to build up a synopsis on the delivery strategies currently developed.

From the clinical editor

This review discusses recent progress and pertinent limiting factors related to the use of siRNA-s as efficient protein-specific "silencing" agents, focusing on targeted delivery not only to cells of interest, but to the proper intracellular destination.

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Read article at publisher's site: https://doi.org/10.1016/j.nano.2013.11.018

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