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Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment

Stimuli-responsive gene delivery vectors

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Abstract

Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

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Acknowledgments

The authors would like to thank Politecnico di Milano (FARB 2011) and MIUR (FIRB Futuro in Ricerca 2008—Grant Number RBFR08XH0H) for providing financial support.

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Authors and Affiliations

  1. Research Unit Milano Politecnico, INSTM (National Interuniversity Consortium of Materials Science and Technology), via Mancinelli 7, 20131, Milan, Italy

    Daniele Pezzoli & Gabriele Candiani

  2. Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, via Mancinelli 7, 20131, Milan, Italy

    Gabriele Candiani

  3. Centro Interuniversitario di Ricerca in Biotecnologie Proteiche “The Protein Factory”, Politecnico di Milano, CNR-ICRM Milano, and Università degli Studi dell’Insubria, via Mancinelli 7, 20131, Milan, Italy

    Gabriele Candiani

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  1. Daniele Pezzoli
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Correspondence to Gabriele Candiani.

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Pezzoli, D., Candiani, G. Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment. J Nanopart Res 15, 1523 (2013). https://doi.org/10.1007/s11051-013-1523-7

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