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RNAi-Based Nano-Oncologicals: Delivery and Clinical Applications

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Nano-Oncologicals

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

RNA-modulating nanodrugs triggering RNA interference (RNAi) such as small interfering RNA (siRNA), microRNA (miRNA), or their counteracting antagomirs have the potential to treat an extensive range of diseases, including cancer. The delivery of these small therapeutic nucleic acids is still a major challenge. RNA biodegradation and rapid clearance from systemic circulation, immune responses, and weak targeting to the disease tissue are obstacles to be addressed. For successful delivery, several strategies have been developed in the last years. Chemical modifications of RNA nucleotides and oligonucleotide backbones have been shown to improve stability and to reduce immunogenicity. In addition, cationic polymers or lipid-based systems may serve as delivery vesicles to protect and to transport the RNAi-modulating nucleic acid to its site of action but still require further improvements. Sequence-defined oligomers can be designed which combine multifunctionality with precision. Functional domains for increased binding of the nucleic acid, receptor targeting and protection of polyplexes against undesired interactions, or enhancing the endosomal escape into the cytosol can be assembled into potent and precise nucleic acid carriers. First RNAi based drugs have recently entered human cancer clinical trials and show in several cancer types encouraging hints for efficacy in the absence of toxicity.

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Acknowledgments

Funding of related research of Katharina Müller and Ernst Wagner by DFG SFB 1032 project B4 is gratefully acknowledged.

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  1. Pharmaceutical Biotechnology, Center for System-Based Drug Research, Center for Nanoscience (CeNS), and Nanosystems Initiative Munich (NIM), Ludwig-Maximilians University, Butenandtstrasse 5-13, 81377, Munich, Germany

    Katharina Müller & Ernst Wagner

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  1. Katharina Müller
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  2. Ernst Wagner
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Correspondence to Katharina Müller .

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  1. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Department of Pharmacy and Pharmaceutical Technology and the Health Research Institute of Santiago de, Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain

    Maria José Alonso

  2. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Department of Pharmacy and Pharmaceutical Technology and the Health Research Institute of Santiago de, Compostela (IDIS), Universidad de Santiago de Compostela, Santiago de Compostela, Spain

    Marcos Garcia-Fuentes

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Müller, K., Wagner, E. (2014). RNAi-Based Nano-Oncologicals: Delivery and Clinical Applications. In: Alonso, M., Garcia-Fuentes, M. (eds) Nano-Oncologicals. Advances in Delivery Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-08084-0_9

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