A new approach is adopted to treat primary immunodeficiency disorders, such as the severe combined immunodeficiency (SCID; e.g., adenosine deaminase SCID [ADA-SCID] and IL-2 receptor X-linked severe combined immunodeficiency [SCID-X1]). The success, along with the feasibility of gene therapy, is undeniable when considering the benefits recorded for patients with different classes of diseases or disorders needing treatment, including SCID-X1 and ADA-SCID, within the last two decades. β-Thalassemia and sickle cell anemia are two prominent monogenic blood hemoglobin disorders for which a solution has been sought using gene therapy. For instance, transduced autologous CD34+ HSCs via a self-inactivating (SIN)-Lentivirus (LV) coding for a functional copy of the β-globin gene has become a feasible procedure. adeno-associated virus (AAV) vectors have found application in ocular gene transfer in retinal disease gene therapy (e.g., Leber’s congenital amaurosis type 2), where no prior treatment existed. In neurodegenerative disorders, successes are now reported for cases involving metachromatic leukodystrophy causing severe cognitive and motor damage. Gene therapy for hemophilia also remains a viable option because of the amount of cell types that are capable of synthesizing biologically active FVIII and FIX following gene transfer using AAV vectors in vivo to correct hemophilia B (FIX deficiency), and it is considered an ideal target, as proven in preclinical studies. Recently, the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 gene-editing tool has taken a center stage in gene therapy research and is reported to be efficient and highly precise. The application of gene therapy to these areas has pushed forward the therapeutic clinical application.

中文翻译：

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PID，血红蛋白，眼病，神经退行性疾病和血友病B疾病的基因治疗

采用了一种新方法来治疗原发性免疫缺陷疾病，例如严重的联合免疫缺陷病（SCID；例如，腺苷脱氨酶SCID [ADA-SCID]和IL-2受体X连锁的严重联合免疫缺陷病[SCID-X1]）。考虑过去20年中为需要治疗的不同类别疾病或病症（包括SCID-X1和ADA-SCID）的患者所记录的益处，无可否认的是，基因疗法的成功与成功。β-地中海贫血和镰状细胞性贫血是两种主要的单基因血液血红蛋白疾病，已通过基因疗法寻求解决方案。例如，通过编码β-珠蛋白基因功能性拷贝的自灭活（SIN）-慢病毒（LV）转导的自体CD34 + HSC已成为可行的方法。腺相关病毒（AAV）载体已在视网膜疾病基因治疗（例如，Leber 2型先天性黑ur病2型）的眼科基因转移中得到应用，目前尚无治疗方法。在神经退行性疾病中，据报道成功治疗了涉及导致严重认知和运动损伤的异色性白细胞营养不良的病例。血友病的基因治疗也仍然是可行的选择，因为在体内使用AAV载体纠正血友病B（FIX缺乏症）后，能够合成具有生物活性的FVIII和FIX的细胞类型数量众多，并且它被认为是理想的靶点，如临床前研究中所证明。最近，聚簇的规则间隔的回文重复序列（CRISPR）/ CRISPR相关蛋白9基因编辑工具在基因治疗研究中处于中心位置，据报道是高效且高度精确的。基因治疗在这些领域的应用推动了治疗性临床应用。