Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8845-8849. doi: 10.1073/pnas.1914408117. Epub 2020 Apr 6.
The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently, in multicellular organisms including plants and animals. However, the addition of new building blocks to the genetic code of tissues from human origin has not yet been achieved. To this end, we report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice.
非天然氨基酸(ncAAs)的遗传掺入已在细菌、酵母和哺乳动物细胞中实现,最近也在包括植物和动物在内的多细胞生物中实现。然而,尚未在源自人类的组织的遗传密码中添加新的构建块。为此,我们报告了一种基于自我复制的 Epstein-Barr 病毒的附加体载体,用于在人类造血干细胞中长期编码 ncAAs,并在小鼠中重建这种经过基因工程改造的造血系统。