Center for Precision Medicine, China Medical University Hospital, Taichung City, Taiwan.
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei City, Taiwan.
J Biomed Sci. 2024 Aug 13;31(1):79. doi: 10.1186/s12929-024-01070-1.
Gene therapy has made considerable strides in recent years. More than 4000 protein-coding genes have been implicated in more than 6000 genetic diseases; next-generation sequencing has dramatically revolutionized the diagnosis of genetic diseases. Most genetic diseases are considered very rare or ultrarare, defined here as having fewer than 1:100,000 cases, but only one of the 12 approved gene therapies (excluding RNA therapies) targets an ultrarare disease. This article explores three gene supplementation therapy approaches suitable for various rare genetic diseases: lentiviral vector-modified autologous CD34 hematopoietic stem cell transplantation, systemic delivery of adeno-associated virus (AAV) vectors to the liver, and local AAV delivery to the cerebrospinal fluid and brain. Together with RNA therapies, we propose a potential business model for these gene therapies.
近年来，基因治疗取得了相当大的进展。已有超过 4000 个蛋白质编码基因与 6000 多种遗传疾病相关联；下一代测序技术极大地改变了遗传疾病的诊断方式。大多数遗传疾病被认为非常罕见或超罕见，这里定义为少于 1:100000 例，但在 12 种已批准的基因疗法（不包括 RNA 疗法）中，只有一种针对超罕见疾病。本文探讨了三种适合各种罕见遗传疾病的基因补充治疗方法：慢病毒载体修饰的自体 CD34 造血干细胞移植、腺相关病毒（AAV）载体全身递送至肝脏，以及局部 AAV 递送至脑脊液和大脑。结合 RNA 疗法，我们为这些基因疗法提出了一种潜在的商业模式。
