| Two reports have shown that mammalian artificial chromosomes (MAC) can
be constructed from cloned human centromere DNA and telomere repeats,
proving the principle that chromosomes can form from naked DNA molecules
transfected into human cells. The MACs were mitotically stable, low copy
number and bound antibodies associated with active centromeres. As a step
toward second-generation MACs, yeast and bacterial cloning systems will
have to be adapted to achieve large MAC constructs having a centromere,
two telomeres, and genomic copies of mammalian genes. Available
construction techniques are discussed along with a new P1 artificial
chromosome (PAC)-derived telomere vector (pTAT) that can be joined to
other PACs in vitro, avoiding a cloning step during which large repetitive
arrays often rearrange. The PAC system can be used as a route to further
define the optimal DNA elements required for efficient MAC formation, to
investigate the expression of genes on MACs, and possibly to develop
efficient MAC-delivery protocols. BioEssays 1999;21:76-83. © 1999 John
Wiley & Sons, Inc. |