Department of Pediatrics, Divisions of Cancer Biology, Hematology/Oncology, Human Gene Therapy, Stanford University, Stanford, California, USA.
Ann N Y Acad Sci. 2011 Dec;1246:131-40. doi: 10.1111/j.1749-6632.2011.06314.x.
The devastating nature of primary immunodeficiencies, the ability to cure primary immunodeficiencies by bone marrow transplantation, the ability of a small number of gene-corrected cells to reconstitute the immune system, and the overall suboptimal results of bone marrow transplantation for most patients with primary immunodeficiencies make the development of gene therapy for this class of diseases important. While there has been clear clinical benefit for a number of patients from viral-based gene therapy strategies, there have also been a significant number of serious adverse events, including the development of leukemia, from the approach. In this review, I discuss the development of nuclease-stimulated, homologous recombination-based approaches as a novel gene therapy strategy for the primary immunodeficiencies.
原发性免疫缺陷的破坏性、骨髓移植治愈原发性免疫缺陷的能力、少量基因修正细胞重建免疫系统的能力，以及骨髓移植对大多数原发性免疫缺陷患者总体效果不佳，这些都使得为这类疾病开发基因治疗方法变得重要。虽然基于病毒的基因治疗策略已经使许多患者明显受益，但该方法也出现了许多严重的不良事件，包括白血病的发生。在这篇综述中，我讨论了基于核酸酶刺激的同源重组的方法作为原发性免疫缺陷的一种新的基因治疗策略的发展。
