nano and microtechnologies for the delivery of oligonucleotides with gene silencing properties纳米制造技术和交付的寡核苷酸基因沉默的属性.pdfVIP

Molecules 2009, 14, 2801-2823; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Nano and Microtechnologies for the Delivery of Oligonucleotides with Gene Silencing Properties Giuseppe De Rosa * and Maria Immacolata La Rotonda Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; E-mail: larotond@unina.it (M.I.L.R.) * Author to whom correspondence should be addressed; E-mail: gderosa@unina.it Received: 30 June 2009; in revised form: 22 July 2009 / Accepted: 27 July 2009 / Published: 29 July 2009 Abstract: Oligonucleotides (ONs) are synthetic fragments of nucleic acid designed to modulate the expression of target proteins. DNA-based ONs (antisense, antigene, aptamer or decoy) and more recently a new class of RNA-based ONs, the small interfering RNAs (siRNAs), have gained great attention for the treatment of different disease states, such as viral infections, inflammation, diabetes, and cancer. However, the development of therapeutic strategies based on ONs is hampered by their low bioavailability, poor intracellular uptake and rapid degradation in biological fluids. The use of a non-viral carrier can be a powerful tool to overcome these drawbacks. Lipid or polymer-based nanotechnologies can improve biological stability and cellular uptake of ONs, w