Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Centro de Investigaciones Cardiovasculares "Dr. Horacio Cingolani," Universidad Nacional de La Plata-CONICET, La Plata, Argentina.
Methods Mol Biol. 2022;2573:235-248. doi: 10.1007/978-1-0716-2707-5_18.
One of the greatest barriers for the use of adeno-associated vectors (AAV) in gene therapy is the presence of pre-existing antibodies against AAV in the general population. Since many of the anti-AAV antibodies have the ability to neutralize the transduction target tissues, even patients with low antibody titers must be excluded from clinical trials or therapy. In recent years, various methods have been proposed to overcome this problem, unfortunately with limited success. In this chapter, we describe in detail a protocol for hemapheresis with an immunoadsorption matrix to remove specifically anti-AAV antibodies in an in vivo rat model. Furthermore, this chapter describes in detail the methods to determine the efficiency of hemapheresis and immunoadsorption.
腺相关病毒(AAV)在基因治疗中的应用面临的最大障碍之一是普通人群中存在针对 AAV 的预先存在的抗体。由于许多抗 AAV 抗体具有中和转导靶组织的能力,因此即使抗体滴度较低的患者也必须从临床试验或治疗中排除。近年来,已经提出了各种方法来克服这个问题,但遗憾的是,这些方法的效果有限。在本章中,我们详细描述了一种用免疫吸附基质进行血液分离以去除体内大鼠模型中特异性抗 AAV 抗体的方案。此外,本章还详细描述了确定血液分离和免疫吸附效率的方法。