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Oligonucleotide delivery: a patent review (2010 – 2013)

, &
Pages 801-819 | Published online: 05 May 2014
 

Abstract

Introduction: The use of aptamers, antisense technology and RNA interference has allowed nucleic acids to be considered as promising alternatives to classical drugs. However, nucleic acids face several obstacles in the creation of effective nucleic acid drugs. The development of these approaches has strengthened the pipeline with an increasing number of these therapies in clinical trials.

Areas covered: This review covers research and patent literature from the last three years, focusing on the development of safe and effective non-viral drug delivery systems for the treatment of diseases such as cancer or genetic disorders by using oligonucleotides.

Expert opinion: The therapeutic applications of oligonucleotides have overcome multiple obstacles, especially in biodistribution and cellular internalization. Cationic lipids are the most used vehicles for the preparation of novel formulations. Combinatorial libraries of these compounds and the use of solid lipid nanoparticles carrying these synthetic cationic lipids (cholesterol and PEG) have enhanced cellular uptake and biocompatibility of nucleic acids. Besides this extensive use, synthesis of oligonucleotides covalently linked to lipids has also emerged as a promising alternative to formulations. The use of peptides alone or in combination with lipids is an expanding field for oligonucleotide delivery. Polymeric platforms are also good candidates as they showed improved cellular uptake, biodegradability, biocompatibility and the possibility of incorporating several components, such as ligands for receptor-mediated endocytosis and molecules, to facilitate endosomal escape. Finally, nanomaterials may also play an important role in the future. The last developments showed improvement in in vivo efficacy, thus gaining a foothold in therapeutics.

Acknowledgments

S Grijalvo and A Aviñó have contributed equally to this work. Dedicated to the memory of Dr. Francisco Sánchez-Baeza.

Notes

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