Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i, 252 50 Vestec, Czech Republic.
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, v.v.i, 252 50 Vestec, Czech Republic.
Cells. 2024 May 27;13(11):920. doi: 10.3390/cells13110920.
Diamond-Blackfan anemia (DBA) is a rare genetic disorder affecting the bone marrow's ability to produce red blood cells, leading to severe anemia and various physical abnormalities. Approximately 75% of DBA cases involve heterozygous mutations in ribosomal protein (RP) genes, classifying it as a ribosomopathy, with RPS19 being the most frequently mutated gene. Non-RP mutations, such as in GATA1, have also been identified. Current treatments include glucocorticosteroids, blood transfusions, and hematopoietic stem cell transplantation (HSCT), with HSCT being the only curative option, albeit with challenges like donor availability and immunological complications. Gene therapy, particularly using lentiviral vectors and CRISPR/Cas9 technology, emerges as a promising alternative. This review explores the potential of gene therapy, focusing on lentiviral vectors and CRISPR/Cas9 technology in combination with non-integrating lentiviral vectors, as a curative solution for DBA. It highlights the transformative advancements in the treatment landscape of DBA, offering hope for individuals affected by this condition.
Diamond-Blackfan 贫血（DBA）是一种罕见的遗传性疾病，影响骨髓产生红细胞的能力，导致严重贫血和各种身体异常。大约 75%的 DBA 病例涉及核糖体蛋白（RP）基因的杂合突变，将其归类为核糖体病，其中 RPS19 是最常突变的基因。也已经确定了非-RP 突变，如 GATA1。目前的治疗方法包括糖皮质激素、输血和造血干细胞移植（HSCT），HSCT 是唯一的治愈方法，但存在供体可用性和免疫并发症等挑战。基因治疗，特别是使用慢病毒载体和 CRISPR/Cas9 技术，成为一种有前途的替代方法。这篇综述探讨了基因治疗的潜力，重点介绍了慢病毒载体和 CRISPR/Cas9 技术与非整合慢病毒载体的结合，作为 DBA 的一种治愈方法。它突出了 DBA 治疗领域的变革性进展，为受这种疾病影响的个体带来了希望。
