Mammalian artificial chromosomes as tools for gene therapy

Mammalian artificial chromosomes (MACs) represent powerful tools for human gene therapy and animal transgenesis. First-generation linear genomic human artificial chromosomes (HACs) and circular chimeric genomic/viral mouse artificial episomal chromosomes (MAECs) have been developed. HACs have been shuttled from human into mouse embryonal stem cells and human trans-chromosomic mice have been generated. The potential of new genetic cis-elements and epigenetic phenomena for de novo segregation and replication activities on MACs are points for discussion. Once the size and delivery constraints of HACs are circumvented, therapeutic applications will be numerous, particularly for recessive syndromes involving large genes and multigenic diseases.