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[摘要]：Background: Although cystic fibrosis (CF) seems a good candidate for gene therapy (GT), 15 years of intense investigations and a number of clinical trials have not yet produced a viable clinical GT strategy. Objective: To review the strategies used to optimize the current GT vectors, to overcome the extra- and cellular barriers to efficient gene delivery to the CF airways, and the poor long-term persistence of gene expression. Methods: We describe a selected set of patents, which were published in the last 5 years (2003 - 2008), with the aim of covering the issues related to GT and the airways; however, in some cases, they are intended for a broader use than CFGT. World Intellectual Property Organization (WIPO), the European network of patent databases, and the US Patent Office were queried. Results/conclusions: Novel biodegradable and biocompatible non-viral GT vectors have been characterized and used for gene transfer into the airways, along with physical methods to enhance their concentration at the level of airway epithelium. Less immunogenic and more efficient adeno-associated viral vectors are being studied, whereas integrating lentiviral viruses are currently investigated for their potential use to give prolonged gene expression. Methods for overcoming the mucus barrier and for increasing accessibility to the basolateral receptors have been described. Although a wealth of GT vectors has been produced, their fabrication, storage and administration are still critical issues, and these shortcomings are tackling translation of laboratory non-viral and viral vectors to the clinic. Thus, in the near future, we expect new developments in GT vector technology, above all of delivery, expression and safety. These improvements, along with better comprenhension of CF lung disease pathophysiology, will aid CFGT to achieve clinical benefits in CF patients. |
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