Advances towards targetable adenovirus vectors for gene therapy.
Advances towards targetable adenovirus vectors for gene therapy.
复制标题
用于基因治疗的靶向腺病毒载体的进展。
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
P. Roelvink
中科院分区：
文献类型：
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作者：
D. Einfeld;P. Roelvink
基于腺病毒的载体可以通过与细胞表面上的特异性受体结合而启动的进入过程将治疗基因有效地转移到细胞中。最常用的Ad载体的受体包括科萨基和腺病毒受体（CAR）和ω-整联蛋白。如果可以调节基因转移的特异性以增强治疗基因在转移组织中的表达并避免非靶组织，则AD载体的治疗应用可以扩大。使用几种方法已经成功地将Ad载体重新靶向到新型受体。讨论了具体办法的优点和挑战。这些重靶向Ad载体的体内评价已经给出了有希望的结果，但也突出了实现有效靶向基因递送的额外挑战。除了影响与天然受体、CAR和整联蛋白的相互作用的那些修饰之外，可能还需要其他修饰，以避免在全身给药后有效去除循环载体的清除机制，并避免在非靶组织如肝脏中的基因转移。开发解决这些问题并可靶向新型受体的Ad载体将使目前不可行的应用中的疾病部位的基因递送成为可能。
Adenovirus-based vectors can efficiently transfer therapeutic genes into cells through an entry process that is initiated be binding to specific receptors on the cell surface. The receptors for the most commonly used Ad vectors include both the Coxsackie and adenovirus receptor (CAR) and omega-integrins. Therapeutic applications of AD vectors could be expanded if the specificity of gene transfer could be modulated to enhance expression of a therapeutic gene in transfer tissues and avoid non-target tissues. Ad vectors have been successfully retargeted to novel receptors using several approaches. The merits and challenges of specific approaches are discussed. In vivo evaluation of these retargeted Ad vectors has given promising results but has also highlighted additional challenges for achieving efficient targeted gene delivery. Additional modifications beyond those affecting interaction with the native receptors, CAR and integrins may be required both to avoid the clearance mechanisms that effectively remove circulating vector following systemic administration and to avoid gene transfer in non-target tissues such as the liver. Developing Ad vector that address these issues and can be targeted to novel receptors would enable gene delivery at the site of disease in applications that are currently not feasible.