A novel approach in gene therapy was introduced 20 years ago since artificial non-integrative chromosome-based vectors containing gene loci size inserts were engineered. To date, different human artificial chromosomes (HAC) were generated with the use of de novo construction or “top-down” engineering approaches. The HAC-based therapeutic approach includes ex vivo gene transferring and correction of pluripotent stem cells (PSCs) or highly proliferative modified stem cells. The current progress in the technology of induced PSCs, integrating with the HAC technology, resulted in a novel platform of stem cell-based tissue replacement therapy for the treatment of genetic disease. Nowadays, the sophisticated and laborious HAC technology has significantly improved and is now closer to clinical studies. In here, we reviewed the achievements in the technology of de novo synthesized HACs for a chromosome transfer for developing gene therapy tissue replacement models of monogenic human diseases.

自从20年前人工合成了基于非整合染色体的包含基因位点大小插入片段的载体以来，基因治疗中就采用了一种新方法。迄今为止，通过使用从头构建或“自上而下”的工程方法生成了不同的人类人工染色体（HAC）。基于HAC的治疗方法包括离体基因转移和多能干细胞（PSC）或高度增殖的修饰干细胞的校正。诱导型PSC的技术发展与HAC技术相结合，为基于干细胞的组织替代疗法提供了一种新型平台，用于治疗遗传性疾病。如今，复杂而费力的HAC技术已经得到了显着改善，并且越来越接近临床研究。在这里，