肿瘤细胞治疗研究
英文原题：Clinical applications of gene therapy for rare diseases: A review.
罕见病总体给社会带来沉重负担，原因在于其数量众多且总体患病率较高。
罕见病由于其庞大的数量和总体患病率，给社会带来了沉重的负担。其异质性、多样性和本质为管理和治疗带来了严峻的临床挑战。在这篇综述中，我们讨论了基因治疗在罕见病临床应用中的最新进展，重点关注各种病毒和非病毒策略。腺相关病毒（AAV）载体的使用将在Luxturna的背景下讨论，该药获批用于治疗视网膜上皮中RPE65缺陷。Imlygic是一种获批用于治疗难治性转移性黑色素瘤的疱疹病毒载体，将作为针对罕见癌症开发的溶瘤载体的例子。Yescarta和Kymriah将展示逆转录病毒和慢病毒载体在自体体外生产CAR-T 细胞中的应用，该疗法获批用于治疗难治性白血病和淋巴瘤。类似的逆转录病毒和慢病毒技术可应用于自体和造血干细胞，Strimvelis和Zynteglo即为范例，分别获批用于治疗腺苷脱氨酶严重联合免疫缺陷（ADA-SCID）和β-地中海贫血。反义寡核苷酸技术将通过Onpattro和Tegsedi加以重点介绍，这两种RNA干扰药物获批用于家族性转甲状腺素蛋白（TTR）淀粉样变性，以及Spinraza，一种用于脊髓性肌萎缩症（SMA）的剪接转换治疗。通过Zolgensma（一种AAV血清型9载体）和Spinraza，可以对AAV和寡核苷酸疗法在SMA中的有效性进行初步比较。通过这些已上市基因治疗和基因细胞治疗的例子，我们将讨论这些新技术在以往难以治疗的罕见病中日益扩大的应用。
Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and -thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.
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