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• W2479962693 abstract "Publisher Summary This chapter discusses several biological and cellular barriers that pose limitations to the clinical application of nonviral gene delivery systems. The transfer of exogenous DNA into somatic cells is a complex process involving the passage through numerous biological barriers, and is particularly complicated in the case of in vivo applications. These barriers include the extracellular matrix, the cell membrane, the intracellular environment, and also the nuclear envelope. To overcome these barriers, the development of nonviral gene transfer systems tends toward multicomponent structures that may contain (poly)cationic elements for DNA condensation, lipidic compounds for enhanced protection and affinity to cell membranes, and additional ligands for cell targeting and intracellular processing. Because of their structural and functional properties, they are described as artificial virus-like particles and will be known as heteroplexes in analogy to lipo- and polyplexes. It is claimed that heteroplexes can circumvent the current limiting factors of viral vectors such as immunogenicity, size limitations of the transgene, potential mutation to replication-competent recombinant viruses, and the expensive production. Abstract The clinical success of nonviral gene therapy will depend on our ability to design efficient and targeted gene delivery systems. It is now understood that the gene transfer mechanism is a complicated process during which the vector has to overcome numerous biological and cellular barriers. As a consequence, nonviral gene delivery systems tend to multicomponent complexes containing various biofunctional elements. The ultimate goal is to circumvent inhibitory effects and to take advantage of cellular transport and degradation processes. The challenges for the development of novel systems are multiple. A better understanding of the molecular processes underlying the transfection mechanism is required. It is not clear through which mechanism the vector enters the cell and finally reaches the nucleus. In addition, cellular factors limiting the transfection process should also be identified. Because of the critical biological role of DNA, the existence of specific protective cellular mechanisms, as the result of the massive uptake of exogenous DNA, is expected. Another important issue is the influence of physicochemical properties of DNA complexes such as size, condensation rate and charge on the transfection process. These parameters are of contradictory effects depending on the particular gene transfer step. Optimization of the transfection system thus comprises chemical modification and/or incorporation of functional elements as well as control of the physicochemical parameters of the complex during the transfection process. The controlled assembly of a multicomponent system and the proper unfolding of its functional elements present a considerable challenge. Their success will require a close cooperation between biologists and material scientists." @default.
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• W2479962693 date "2006-01-01" @default.
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• W2479962693 title "Biological and Cellular Barriers Limiting the Clinical Application of Nonviral Gene Delivery Systems**This paper was first published in Gene Therapy, 2002 February, 9(3), 157–167." @default.
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• W2479962693 doi "https://doi.org/10.1016/b978-044452806-3/50006-8" @default.
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