From kilobases to megabases: Design and delivery of large DNA constructs into mammalian genomes

Abstract As DNA synthesis has become cheaper, it has made assembly of larger and larger genes possible. To fully realise this opportunity for a new era of synthetic biology in mammals, a number of gaps are beginning to be addressed in the design, synthesis, assembly and delivery of DNA constructs into large genomes. While current DNA design software is still inadequate for complex mammalian genomes, editing large bacterial artificial chromosomes is now easier. Newer viral technologies, such as herpes simplex virus, have been adapted for assembly of mammalian artificial chromosomes. Further advances in genome engineering, such as CRISPR- and Retron-based systems, will simplify targeted insertion of big DNA – all promising an exciting future for this field.