Rare monogenic disorders are a group of single-gene-mutated diseases that have a low incidence rate (less than 0.5‰) and eventually lead to patient disability and even death. Due to the relatively low number of people affected, these diseases typically fail to attract a great deal of commercial investment and research interest, and the affected patients thus have unmet medical needs. Advances in genomics biology, gene editing, and gene delivery can now offer potentially effective options for treating rare monogenic diseases. Herein, we review the application of gene therapy strategies (traditional gene therapy and gene editing) against various rare monogenic diseases with nuclear or mitochondrial gene mutations, including eye, central nervous system, pulmonary, systemic, and blood cell diseases. We summarize their pathologic features, address the barriers to gene delivery for these diseases, discuss available therapies in the clinic and in clinical trials, and sum up in-development gene delivery systems for various rare monogenic disorders. Finally, we elaborate the possible directions and outlook of gene therapy for rare monogenic disorders.

罕见的单基因疾病是一组发生率低（小于0.5‰）并最终导致患者残疾甚至死亡的单基因突变疾病。由于受影响的人数相对较少，这些疾病通常无法吸引大量的商业投资和研究兴趣，因此受影响的患者的医疗需求未得到满足。基因组生物学、基因编辑和基因传递方面的进展现在可以为治疗罕见的单基因疾病提供潜在的有效选择。在此，我们回顾了基因治疗策略（传统基因治疗和基因编辑）在各种具有核或线粒体基因突变的罕见单基因疾病中的应用。，包括眼睛、中枢神经系统、肺部、全身和血细胞疾病。我们总结了它们的病理特征，解决了这些疾病的基因传递障碍，讨论了临床和临床试验中的可用疗法，并总结了各种罕见单基因疾病的正在开发的基因传递系统。最后，我们阐述了罕见单基因疾病基因治疗的可能方向和前景。