Odiba Arome Solomon, Okoro Nkwachukwu Oziamara, Durojaye Olanrewaju Ayodeji, Wu Yanjun
Molecular Biology Laboratory, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, Nanning, China.
Department of Biochemistry, College of Life Science and Technology, Guangxi University, Nanning, China.
Open Life Sci. 2021 May 3;16(1):431-441. doi: 10.1515/biol-2021-0033. eCollection 2021.
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 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.
一种新的方法被用于治疗原发性免疫缺陷疾病，例如严重联合免疫缺陷（SCID；例如，腺苷脱氨酶SCID [ADA - SCID] 和IL - 2受体X连锁严重联合免疫缺陷 [SCID - X1]）。考虑到在过去二十年中为不同类型需要治疗的疾病或病症（包括SCID - X1和ADA - SCID）患者所记录的益处，基因治疗的成功以及可行性是不可否认的。β地中海贫血和镰状细胞贫血是两种突出的单基因血液血红蛋白疾病，人们一直在寻求使用基因治疗来解决这两种疾病。例如，通过编码β - 珠蛋白基因功能拷贝的自我失活（SIN）慢病毒（LV）转导自体CD34 + 造血干细胞已成为一种可行的方法。腺相关病毒（AAV）载体已在视网膜疾病基因治疗（例如，2型莱伯先天性黑蒙）的眼部基因转移中得到应用，此前该疾病并无有效治疗方法。在神经退行性疾病方面，现已报道在涉及导致严重认知和运动损伤的异染性脑白质营养不良的病例中取得了成功。血友病的基因治疗也仍然是一个可行的选择，因为使用AAV载体进行基因转移后，有多种细胞类型能够合成具有生物活性的FVIII和FIX以纠正血友病B（FIX缺乏），并且如临床前研究所证明的，它被认为是一个理想的治疗靶点。最近，成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关蛋白9基因编辑工具在基因治疗研究中占据了核心地位，据报道该工具高效且高度精确。基因治疗在这些领域的应用推动了其临床治疗应用的发展。
