Fliervoet Lies A L, Engbersen Johan F J, Schiffelers Raymond M, Hennink Wim E, Vermonden Tina
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
J Mater Chem B. 2018 Sep 28;6(36):5651-5670. doi: 10.1039/c8tb01795f. Epub 2018 Aug 31.
The potential of gene therapy for the treatment for chronic and life-threatening diseases has been seen for a long time, but widespread applications are still hampered by the difficulties to deliver the highly charged and large nucleic acid molecules to their intracellular targets. More recently, investigators have been aiming for local delivery of nucleic acids mostly by the use of hydrogels. In this way, in vivo efficacy can be enhanced by avoiding the target transport challenges and at the same time limit off-target effects. In these systems, nucleic acids are entrapped within hydrogels, either as conjugates or as polyplex particles, for local and controlled release. There are numerous design features in the selection of polymers, for both particle and hydrogel formation that should be considered to achieve efficient local nucleic acid delivery. Therefore, this review focusses on the rational design of polymeric and hydrogel materials for local gene therapy applications.
长期以来，人们一直认为基因疗法在治疗慢性和危及生命的疾病方面具有潜力，但由于难以将高电荷的大分子核酸递送至细胞内靶点，其广泛应用仍然受到阻碍。最近，研究人员主要致力于通过使用水凝胶实现核酸的局部递送。通过这种方式，可避免靶点转运挑战，从而提高体内疗效，同时限制脱靶效应。在这些系统中，核酸以缀合物或多聚体颗粒的形式包裹在水凝胶中，实现局部和可控释放。在选择用于形成颗粒和水凝胶的聚合物时，有许多设计特点需要考虑，以实现高效的局部核酸递送。因此，本综述聚焦于用于局部基因治疗应用的聚合物和水凝胶材料的合理设计。
