Immunological ignorance allows long-term gene expression after perinatal recombinant adeno-associated virus-mediated gene transfer to murine airways.
Immunological ignorance allows long-term gene expression after perinatal recombinant adeno-associated virus-mediated gene transfer to murine airways.
复制标题
免疫学上的无知使得围产期重组腺相关病毒介导的基因转移至小鼠气道后长期基因表达。
作者：
M. Carlon;D. Vidovic;J. Dooley;M. M. D. da Cunha;M. Maris;Y. Lampi;J. Toelen;C. Van den Haute;V. Baekelandt;J. Deprest;E. Verbeken;A. Liston;R. Gijsbers;Z. Debyser
肺的基因疗法有可能治疗危及生命的疾病，如囊性纤维化和α(1)-抗胰蛋白酶或表面活性物质缺乏症。成功的基因治疗的一个主要障碍是针对转基因和/或病毒载体的免疫反应的发展。我们假设，通过在围产期以呼吸道为靶点，可以防止由于免疫系统的不成熟而诱导针对载体颗粒的免疫反应，进而允许在成年后重复进行基因转移，以确保基因的长期表达。因此，我们在最初的围产期基因转移后3个月和6个月将重组腺相关病毒载体血清5型(rAAV2/5)重新注射到小鼠呼吸道。我们的发现表明，围产期rAAV2/5介导的基因转移到呼吸道可以避免强烈的免疫反应。这种免疫学上的无知允许在成年后的生活中重新管理自体载体，导致高达7个月的有效和稳定的基因转移，而没有转基因表达减少的证据。总之，这些数据为进一步探索肺部疾病的围产期基因治疗提供了基础，这些疾病的基因表达水平高达7个月。
Gene therapy of the lung has the potential to treat life-threatening diseases such as cystic fibrosis and α(1)-antitrypsin or surfactant deficiencies. A major hurdle for successful gene therapy is the development of an immune response against the transgene and/or viral vector. We hypothesized that by targeting the airways in the perinatal period, induction of an immune response against the vector particle could be prevented because of immaturity of the immune system, in turn allowing repeated gene transfer later in adult life to ensure long-term gene expression. Therefore, we readministered recombinant adeno-associated viral vector serotype 5 (rAAV2/5) to mouse airways 3 and 6 months after initial perinatal gene transfer. Our findings demonstrate that perinatal rAAV2/5-mediated gene transfer to the airways avoids a strong immune response. This immunological ignorance allows the readministration of an autologous vector later in adult life, resulting in efficient and stable gene transfer up to 7 months, without evidence of a decrease in transgene expression. Together, these data provide a basis to further explore perinatal gene therapy for pulmonary conditions with adequate gene expression up to 7 months.
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影响因子：
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作者：
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DOI：
10.1172/jci15780
发表时间：
2002
期刊：
The Journal of clinical investigation.
影响因子：
--
作者：
Auricchio,Alberto;O'Connor,Erin;Weiner,Daniel;Gao,Guang-Ping;Hildinger,Markus;Wang,Lili;Calcedo,Roberto;Wilson,JamesM
通讯作者：
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