Tsaregorodtseva Tatiana S, Gubaidullina Aigul A, Kayumova Beata R, Shaimardanova Alisa A, Issa Shaza S, Solovyeva Valeriya V, Sufianov Albert A, Sufianova Galina Z, Rizvanov Albert A
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.
Int J Mol Sci. 2025 May 29;26(11):5224. doi: 10.3390/ijms26115224.
Neutralizing antibodies (nAbs) are an important component of the immune system, which plays a dual role in modern medicine. On the one hand, they significantly limit the effectiveness of gene therapy based on viral vectors, reducing the effectiveness of treatment of diseases such as spinal muscular atrophy, which is especially evident with repeated administration of therapeutic vectors. On the other hand, nAbs is a promising tool for combating viral infections. This review systematizes current data on the mechanisms of nAbs formation against AAV vectors, analyzes the factors influencing their production, and discusses strategies to overcome this limitation, including modification of vectors and the development of methods to suppress the immune response. Special attention is paid to the prospects of using nAbs as therapeutic agents against viral infections. The key problems and possible directions of research development in this area are considered, which is important for improving approaches to the treatment of both rare genetic and infectious diseases.
中和抗体(nAbs)是免疫系统的重要组成部分,在现代医学中发挥着双重作用。一方面,它们显著限制了基于病毒载体的基因治疗的有效性,降低了诸如脊髓性肌萎缩症等疾病的治疗效果,在重复施用治疗性载体时尤为明显。另一方面,中和抗体是对抗病毒感染的一种有前景的工具。本综述系统整理了目前关于针对腺相关病毒(AAV)载体的中和抗体形成机制的数据,分析了影响其产生的因素,并讨论了克服这一限制的策略,包括载体修饰和开发抑制免疫反应的方法。特别关注了将中和抗体用作抗病毒感染治疗剂的前景。考虑了该领域研究发展的关键问题和可能的方向,这对于改进罕见遗传疾病和传染病的治疗方法很重要。