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- W2762843152 abstract "The biological risks associated to viral gene therapy limit the full development of viral vectors and pose major concerns to their incorporation into clinical trials. Gene therapy is going to be a main tool for future medicine. Non-viral gene therapy represents a safe alternative to natural viruses for cell targeted gene delivery, although the low gene expression levels achieved by non-viral vectors are a main obstacle for their therapeutic application they present many advantages over viral vectors regarding their safer use and their much lower production costs. Different types of non-viral vectors have been developed up to date, including those based in liposomes, cationic polimers, dendrimers or proteins. Recently, the ?Artificial virus? concept has been proposed to describe nanocomplexes for gene delivery that mimic the viral functions relevant to gene uptake and intracellular trafficking. Among them, those based on proteins and constructed through modular principles allow the incorporation, in a single polypeptide, of different proteins or protein domains with virus-like functions, namely DNA binding and condensation, receptor binding, internalization, endosomal escape, nuclear targeting and uncoating with basic molecular engineering techniques. We have developed a series of protein-only modular vehicles composed by different functional domains that are able to enter cells through specific receptor binding and promotes important levels of transgene expression. We have characterized those vehicles from the physical point of view and ti has reveled many interesting features regarding their internal molecular organization and nanoparticle formation. From the functional point of view, be have described their ability to deliver expressible genes and have deeply investigated the modular protein approach as a very interesting way to design new gene therapy vehicles. In this regard, a new set of modules, called ?therapeutic modules? have been described. This modules confer the final particle with functions not related to crossing barriers or cell trafficking but give the particle therapeutic functions besides the genetic cargo to deliver. In this thesis this approach is discussed with two review articles and demonstrated with three original papers." @default.
- W2762843152 created "2017-10-20" @default.
- W2762843152 creator A5017724356 @default.
- W2762843152 date "2013-01-01" @default.
- W2762843152 modified "2023-09-26" @default.
- W2762843152 title "Development of artificial viruses for gene therapy" @default.
- W2762843152 hasPublicationYear "2013" @default.
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