Expanding the genetic code of the human hematopoietic system

Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8845-8849. doi: 10.1073/pnas.1914408117. Epub 2020 Apr 6.

Abstract

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.

Keywords: Epstein-Barr virus; genetic code expansion; hematopoietic reconstruction; hematopoietic stem cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / genetics*
  • Animals
  • Cell Differentiation / genetics*
  • Fetal Blood / cytology
  • Gene Transfer Techniques
  • Genetic Code
  • Genetic Vectors / genetics*
  • HEK293 Cells
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / physiology*
  • Herpesvirus 4, Human / genetics
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Plasmids / genetics
  • Primary Cell Culture / methods
  • Protein Engineering / methods*
  • Transfection / methods
  • Transplantation Chimera
  • Transplantation, Heterologous / methods

Substances

  • Amino Acids