Haley Rebecca M, Gottardi Riccardo, Langer Robert, Mitchell Michael J
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Drug Deliv Transl Res. 2020 Jun;10(3):661-677. doi: 10.1007/s13346-020-00724-5.
Gene therapy is a powerful tool against genetic disorders and cancer, targeting the source of the disease rather than just treating the symptoms. While much of the initial success of gene delivery relied on viral vectors, non-viral vectors are emerging as promising gene delivery systems for efficacious treatment with decreased toxicity concerns. However, the delivery of genetic material is still challenging, and there is a need for vectors with enhanced targeting, reduced toxicity, and controlled release. In this article, we highlight current work in gene therapy which utilizes the cyclic oligosaccharide molecule cyclodextrin (CD). With a number of unique abilities, such as hosting small molecule drugs, acting as a linker or modular component, reducing immunogenicity, and disrupting membranes, CD is a valuable constituent in many delivery systems. These carriers also demonstrate great promise in combination therapies, due to the ease of assembling macromolecular structures and wide variety of chemical derivatives, which allow for customizable delivery systems and co-delivery of therapeutics. The use of combination and personalized therapies can result in improved patient health-modular systems, such as those which incorporate CD, are more conducive to these therapy types. Graphical abstract.
基因治疗是对抗遗传疾病和癌症的有力工具,它针对疾病的根源而非仅仅治疗症状。虽然基因递送最初的许多成功依赖于病毒载体,但非病毒载体正作为有前景的基因递送系统崭露头角,有望实现有效治疗且降低对毒性的担忧。然而,遗传物质的递送仍然具有挑战性,需要具有增强靶向性、降低毒性和可控释放的载体。在本文中,我们重点介绍了利用环状寡糖分子环糊精(CD)进行基因治疗的当前研究工作。由于具有多种独特能力,如容纳小分子药物、充当连接体或模块化组件、降低免疫原性以及破坏细胞膜等,CD是许多递送系统中的重要组成部分。由于易于组装大分子结构且有多种化学衍生物,这些载体在联合治疗中也显示出巨大潜力,这使得可定制递送系统以及治疗药物的共递送成为可能。联合治疗和个性化治疗的应用可改善患者健康——模块化系统,如那些包含CD的系统,更有利于这些治疗类型。图形摘要。