Artificial design of the genome: from sequences to the 3D structure of chromosomes

Refactoring the genetic code can optimize gene expression, distinguish synthetic from natural genomes, and enable strains to prevent viral infections and genetic information leakage.The artificial design of noncoding regions can enhance genome stability and flexibility while ensuring the functionality of the genome.Genome reduction can provide a new approach for exploring genome components and their interactions, thereby enabling a more comprehensive understanding of the genome.Modification of the 3D structure of synthetic chromosomes enables the regulation of gene expression without modifying the DNA sequence. Genome design is the foundation of genome synthesis, which provides a new platform for deepening our understanding of biological systems by exploring the fundamental components and structure of the genome. Artificial genome designs can endow unnatural genomes with desired functions. We provide a comprehensive overview of genome design principles ranging from DNA sequences to the 3D structure of chromosomes. Furthermore, we highlight applications of genome design in gene expression, genome structure, genome function, and biocontainment, and discuss the potential of artificial intelligence (AI) in genome design. Genome design is the foundation of genome synthesis, which provides a new platform for deepening our understanding of biological systems by exploring the fundamental components and structure of the genome. Artificial genome designs can endow unnatural genomes with desired functions. We provide a comprehensive overview of genome design principles ranging from DNA sequences to the 3D structure of chromosomes. Furthermore, we highlight applications of genome design in gene expression, genome structure, genome function, and biocontainment, and discuss the potential of artificial intelligence (AI) in genome design.