Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?

dc.contributor.authorGuo, Jianfeng
dc.contributor.authorBourre, Ludovic
dc.contributor.authorSoden, Declan
dc.contributor.authorO'Sullivan, Gerald C.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.date.accessioned2013-01-29T10:16:24Z
dc.date.available2013-01-29T10:16:24Z
dc.date.copyright2011
dc.date.issued2011-07
dc.date.updated2013-01-17T10:49:56Z
dc.description.abstractCancer is one of the most wide-spread diseases of modern times, with an estimated increase in the number of patients diagnosed worldwide, from 11.3 million in 2007 to 15.5 million in 2030 (www.who.int). In many cases, due to the delay in diagnosis and high increase of relapse, survival rates are low. Current therapies, including surgery, radiation and chemotherapy, have made significant progress, but they have many limitations and are far from ideal. Although immunotherapy has recently offered great promise as a new approach in cancer treatment, it is still very much in its infancy and more information on this approach is required before it can be widely applied. For these reasons effective, safe and patient-acceptable cancer therapy is still largely an unmet clinical need. Recent knowledge of the genetic basis of the disease opens up the potential for cancer gene therapeutics based on siRNA. However, the future of such gene-based therapeutics is dependent on achieving successful delivery. Extensive research is ongoing regarding the design and assessment of non-viral delivery technologies for siRNA to treat a wide range of cancers. Preliminary results on the first human Phase I trial for solid tumours, using a targeted non-viral vector, illustrate the enormous therapeutic benefits once the issue of delivery is resolved. In this review the genes regulating cancer will be discussed and potential therapeutic targets will be identified. The physiological and biochemical changes caused by tumours, and the potential to exploit this knowledge to produce bio-responsive ‘smart’ delivery systems, will be evaluated. This review will also provide a critical and comprehensive overview of the different non-viral formulation strategies under investigation for siRNA delivery, with particular emphasis on those designed to exploit the physiological environment of the disease site. In addition, a section of the review will be dedicated to pre-clinical animal models used to evaluate the stability, safety and efficacy of the delivery systems.en
dc.description.sponsorshipScience Foundation Ireland ( Strategic Research Cluster Grant (Irish Drug Delivery Network)); Enterprise Ireland (Commercial Fund Technology Development Grant); Irish Research Council for Science, Engineering and Technology (Embark initiative)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationJianfeng Guo, Ludovic Bourre, Declan M. Soden, Gerald C. O'Sullivan, Caitriona O'Driscoll; (2011) 'Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?'. Biotechnology Advances, 29 (4):402-417. http://dx.doi.org/10.1016/j.biotechadv.2011.03.003en
dc.identifier.doi10.1016/j.biotechadv.2011.03.003
dc.identifier.endpage417en
dc.identifier.issn0734-9750
dc.identifier.issued4en
dc.identifier.journaltitleBiotechnology Advancesen
dc.identifier.startpage402en
dc.identifier.urihttps://hdl.handle.net/10468/934
dc.identifier.volume29en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S073497501100036X
dc.rightsCopyright © 2011, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in International Biotechnology Advances . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biotechnology Advances [413, 1-2, 15 July 2011] DOI: http://dx.doi.org/10.1016/j.biotechadv.2011.03.003en
dc.subjectsiRNA deliveryen
dc.subjectCancer therapyen
dc.subjectNon-viral vectorsen
dc.subject.lcshCancer--Gene therapyen
dc.titleCan non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?en
dc.typeArticle (peer-reviewed)en
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