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用于卵巢癌基因治疗的腺相关病毒

AAV for ovarian cancer gene therapy.

作者信息

Yoo Hee Chan, Lee Sangkil, Park Joong Yull, Lee Eun-Ju

机构信息

College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.

Organoid Medical Center, Chung-Ang University, Seoul, Republic of Korea.

出版信息

Cancer Gene Ther. 2025 Jun 20. doi: 10.1038/s41417-025-00926-4.

Abstract

Recent advancements in ovarian cancer treatment, particularly with PARP inhibitors, have markedly enhanced the recurrence-free interval, shifting the treatment paradigm and increasing treatment success in patients with BRCA mutations or HRD (homologous recombination deficiency). However, a significant proportion of cases experience relapse, resulting in poorer long-term survival rates when compared to other female cancers, such as breast cancer. This review explores the potential of adeno-associated virus (AAV) vectors for gene therapy in ovarian cancer and examines rational gene therapy strategies by categorizing them based on target cells and target genes to determine the most effective approach for ovarian cancer treatment. Specifically, it examines strategies such as anti-angiogenesis and immune modulation, highlighting the strategy of gene supplementation to hinder ovarian cancer progression. Innovations in AAV capsid design now allow for targeted delivery, focusing on ovarian cancer stem cells (CSCs) identified by specific markers. Additionally, leveraging DNA sequencing technologies enhances the identification and incorporation of therapeutic genes into AAV vectors, promising new avenues for ovarian cancer gene therapy.

摘要

卵巢癌治疗的最新进展,尤其是PARP抑制剂的应用,显著延长了无复发生存期,改变了治疗模式,提高了BRCA突变或HRD(同源重组缺陷)患者的治疗成功率。然而,相当一部分病例会复发,与其他女性癌症(如乳腺癌)相比,长期生存率较低。本综述探讨了腺相关病毒(AAV)载体在卵巢癌基因治疗中的潜力,并通过根据靶细胞和靶基因对合理的基因治疗策略进行分类,以确定卵巢癌治疗的最有效方法。具体而言,它研究了抗血管生成和免疫调节等策略,强调了基因补充以阻碍卵巢癌进展的策略。AAV衣壳设计的创新现在允许靶向递送,重点是通过特定标志物鉴定的卵巢癌干细胞(CSCs)。此外,利用DNA测序技术可增强治疗基因的鉴定并将其整合到AAV载体中,为卵巢癌基因治疗开辟了新途径。

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