首个吸入慢病毒基因疗法进入囊性纤维化试验

IF 44.5 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nature biotechnology Pub Date : 2025-03-17 DOI:10.1038/s41587-025-02616-w
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引用次数: 0

摘要

一种基于慢病毒的CFTR基因添加治疗囊性纤维化的潜在的一流治疗方法已经开始临床试验。勃林格殷格翰的基因疗法BI 3720931通过吸入慢病毒载体将跨膜传导调节因子(CFTR)基因的全长拷贝传递到气道上皮细胞中,该基因在囊性纤维化患者中发生突变。CFTR基因的突变会破坏CFTR蛋白的产生,而CFTR蛋白有助于调节进出细胞的氯化物的数量;当缺乏或功能失调时,会导致肺部和胰腺疾病。虽然自20世纪90年代以来已经探索了囊性纤维化的基因治疗,但临床疗效一直很低,主要原因是呼吸细胞对基因的吸收较差,没有基因治疗被批准。现有的囊性纤维化治疗是CFTR调节疗法,旨在纠正CFTR基因产生的功能失调蛋白。BI 3720931将在对现有氯离子通道调节剂(如Vertex Pharmaceuticals的Trikafta)无反应的患者中进行测试,约占患者的10-15%。BI 3720931中使用的吸入慢病毒载体由英国呼吸基因治疗协会开发并优化。该小组将小鼠呼吸道病毒的病毒包膜糖蛋白引入载体,以帮助基因转移到气道上皮细胞。在临床前研究中,该方法导致9-15%的呼吸道上皮细胞表达CFTR -足以提供可能的临床益处-至少2年。在动物模型中,可以在不受宿主免疫反应干扰的情况下多次给药。慢病毒载体也在肺泡基因的临床前测试中,作为α1-抗胰蛋白酶缺乏症的吸入基因疗法,影响肺部和肝脏。其他用于囊性纤维化吸入基因疗法的早期试验包括4D分子治疗公司携带CFTR缩短版本的基于腺相关病毒的基因疗法,以及编码全长CFTR的mRNA疗法,如Vertex的VX-522、ReCode治疗公司的RCT2100和Arcturus治疗公司的ARCT-032。
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First inhaled lentiviral gene therapy enters cystic fibrosis trial
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来源期刊
Nature biotechnology
Nature biotechnology 工程技术-生物工程与应用微生物
CiteScore
63.00
自引率
1.70%
发文量
382
审稿时长
3 months
期刊介绍: Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.
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