MAMMALIAN ARTIFICIAL CHROMOSOMES AS TOOLS FOR GENE-THERAPY

Mammalian artificial chromosomes (MACs) represent powerful tools for h uman gene therapy and animal transgenesis. First-generation linear gen omic human artificial chromosomes (HACs) and circular chimeric genomic /viral mouse artificial episomal chromosomes (MAECs) have been develop ed. HACs have been shuttled from human into mouse embryonal stem cells and human trans-chromosomic mice have been generated. The potential o f new genetic cis-elements and epigenetic phenomena for de novo segreg ation and replication activities on MACs are points for discussion. On ce the size and delivery constraints of HACs are circumvented, therape utic applications will be numerous, particularly for recessive syndrom es involving large genes and multigenic diseases.