Loading...
3 results
Search Results
Now showing 1 - 3 of 3
- Chitosan-Hyaluronic acid hybrid vectors for retinal gene therapyPublication . Oliveira, Ana; Bitoque, Diogo; Silva, Gabriela A.
- Non-viral strategies for ocular gene deliveryPublication . V. Oliveira, Ana; Rosa Da Costa, Ana; Silva, Gabriela A.The success of gene therapy relies on efficient gene transfer and stable transgene expression. The in vivo efficiency is determined by the delivery vector, route of administration, therapeutic gene, and target cells. While some requirements are common to several strategies, others depend on the target disease and transgene product. Consequently, it is unlikely that a single system is suitable for all applications. This review examines current gene therapy strategies, focusing on non-viral approaches and the use of natural polymers with the eye, and particularly the retina, as their gene delivery target. (C) 2017 Elsevier B.V. All rights reserved.
- Human-derived NLS enhance the gene transfer efficiency of chitosanPublication . Bitoque, Diogo; Morais, Joana; Oliveira, Ana; Sequeira, Raquel L.; Calado, Sofia; Fortunato, Tiago M.; Simão, Sónia; Rosa Da Costa, Ana; Silva, Gabriela A.Nuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors.