Sosnowski B A, Gu D L, D'Andrea M, Doukas J, Pierce G F
Selective Genetics Inc, 11035 Roselle St, San Diego, CA 92121, USA.
Curr Opin Mol Ther. 1999 Oct;1(5):573-9.
Adenoviral vectors have proven useful for transducing a variety of cell types. However, both adenoviral resistant cell types and vector-related toxicities (due to non-specific tropism), limit their widespread clinical utility. These limitations can be greatly reduced by targeting adenoviral vectors to alternative cell surface receptors. One ligand family, highly effective at targeting adenoviral vectors, is the family of fibroblast growth factors (FGFs). The FGFs allow a high degree of targeting specificity due to their cognate high affinity FGF receptors, which are expressed on cells undergoing repair and regeneration. Recent publications, reviewed herein, demonstrate that FGF-targeted adenoviruses result in enhanced potency and reduced toxicity, and thus substantially increase the therapeutic index in vivo. As a result, vector delivery through FGF receptors provides the targeting specificity required for successful local and systemic clinical applications of gene therapy.
腺病毒载体已被证明可用于转导多种细胞类型。然而，腺病毒抗性细胞类型和载体相关毒性（由于非特异性嗜性）限制了它们在临床上的广泛应用。通过将腺病毒载体靶向替代细胞表面受体，可以大大减少这些限制。一类在靶向腺病毒载体方面非常有效的配体家族是成纤维细胞生长因子（FGFs）家族。由于其同源的高亲和力FGF受体，FGFs具有高度的靶向特异性，这些受体在进行修复和再生的细胞上表达。本文综述的近期出版物表明，FGF靶向腺病毒可提高效力并降低毒性，从而在体内大幅提高治疗指数。因此，通过FGF受体进行载体递送为基因治疗在局部和全身临床应用的成功提供了所需的靶向特异性。
