Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis
Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis
复制标题
DOI：
10.1172/jci118573
复制
发表时间：
1996-03-15
影响因子：
15.9
通讯作者：
Welsh, MJ
中科院分区：
文献类型：
--
作者：
Zabner, J;Ramsey, BW;Welsh, MJ
囊性纤维化（CF）是一种常见的常染色体隐性遗传病，由CF跨膜传导调节基因突变引起，重组腺病毒有望作为将CF跨膜传导调节基因cDNA转移到气道上皮并纠正Cl-转运缺陷的载体。然而，由于腺病毒介导的基因转移是短暂的，使用腺病毒作为载体治疗CF需要反复给药。因此，我们评估了腺病毒载体对CF患者鼻上皮的重复给药，5次递增剂量至10（10）个感染单位，没有检测到不良反应，所有受试者最初都是血清阳性，但产生了额外的体液免疫反应。载体部分纠正了一些受试者气道上皮Cl-运输的缺陷，尽管受试者之间存在差异，后续给药的纠正较少，可能是因为免疫反应限制了基因转移，未来的工作必须集中在提高效率和逃避宿主防御能力的载体上。
Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator gene, Recombinant adenoviruses have shown promise as vectors for transfer of CF transmembrane conductance regulator cDNA to airway epithelia and correction of the Cl- transport defect, However, because adenovirus-mediated gene transfer is transient, use of adenovirus as a vector for treatment of CF would require repeated administration. Therefore, we evaluated repeat administration of an adenovirus vector to the nasal epithelium of patients with CF with five escalating doses of up to 10(10) infectious units, There were no detectable adverse affects, All subjects were initially seropositive but developed additional humoral immune responses. The vector partially corrected the defect in airway epithelial Cl- transport in some subjects, although there was variability between subjects and there was less correction with subsequent administration, perhaps because the immune response limited gene transfer, Future work must focus on vectors with increased efficiency and with the ability to evade host defenses.