Mammalian Artificial Chromosomes: Prospects for Gene Therapy

A mammalian artificial chromosome would mimic the natural means of transferring genetic information from one cell to another and could be used to carry larger gene complexes than current vector systems can handle, possibly tens of millions of base pairs. A centromere, origins of replication and two telomeres are sufficient to generate a yeast artificial chromosome but it is not known whether mammalian chromosomes require extra features. For gene therapy applications, they would need to be invisible to the immune system and easy to deliver to target cells. Attempts to build such artificial chromosomes are proceeding from both directions: deleting elements of existing human chromosomes and assembling the individual components, although for mammalian chromosomes these have not all been defined molecularly.