PDF(Pubmed)
Abstract：
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.
摘要：
近年来，基因治疗取得了长足的进步。4000多个蛋白质编码基因与6000多种遗传疾病有关；下一代测序极大地彻底改变了遗传疾病的诊断。大多数遗传疾病被认为是非常罕见的或超罕见的，这里定义为少于1:100,000的案例，但在12种已批准的基因疗法(不包括RNA疗法)中,只有一种针对的是超微病变.本文探讨了三种适用于多种罕见遗传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,将腺相关病毒（AAV）载体全身递送至肝脏，和局部AAV递送到脑脊液和大脑。连同RNA疗法,我们为这些基因疗法提出了一个潜在的商业模式。
