Nonviral strategies for gene therapy
Nonviral strategies for gene therapy
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DOI：
10.1038/scientificamerican0697-102
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发表时间：
1997-06-01
影响因子：
3
通讯作者：
Felgner, PL
中科院分区：
文献类型：
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作者：
Felgner, PL
正如西奥多·弗里德曼在本期第96页的“克服基因治疗的障碍”中指出的那样，许多开发基因治疗的努力都是利用修饰的病毒将编码潜在治疗蛋白质的基因穿梭到人类细胞中。目的是诱导被病毒侵入的细胞将基因转移到细胞核。然后，细胞应该“表达”或制造出基因所指定的蛋白质。病毒能够有效地将基因转移到细胞中，因为它们已经进化出了特殊的机制，使它们能够与特定类型的细胞结合，并将其货物有效地运送到细胞内部。然而，将病毒作为基因传递载体或载体的治疗用途带来了问题。一些病毒可以破坏它们感染的细胞的DNA，从而产生潜在的有害结果。此外，可以想象，减弱的病毒可以在体内发生变化并恢复其致病活性。另一个严重的限制是，患者可能会对微生物产生免疫反应。这样的反应可以很快使基因治疗无效，因为它们可能会在治疗基因有机会帮助患者之前摧毁病毒本身或杀死受感染的细胞。
As Theodore Friedmann notes in “Overcoming the Obstacles to Gene Therapy” on page 96 of this issue, many efforts at developing gene therapy employ modified viruses to shuttle into human cells genes coding for potentially therapeutic proteins. The aim is to induce cells that are invaded by a virus to transfer the gene to the cell nucleus. The cells should then “express,” or manufacture, the needed protein specified by the gene.Viruses are effective at transferring genes into cells because they have evolved specialized mechanisms that allow them to bind to specific types of cells and to deliver their cargo efficiently into the cellular interior. Yet the therapeutic use of viruses as gene delivery vehicles, or vectors, entails problems. Some viruses can disrupt the DNA of the cells they infect, with potentially harmful results. Furthermore, weakened viruses can conceivably change inside the body and regain their pathogenic activity. An additional serious limitation is that a patient may generate an immune response to the microbe. Such responses can quickly make a gene therapy useless, because they may either destroy the virus itself or possibly kill the infected cells before the therapeutic gene has a chance to help a patient.