Human Artificial Chromosomes

Human artificial chromosomes must contain the same essential functional and stabilizing regions as do normal chromosomes. They must, for example, contain telomeric regions at the end of each the chromosome strand. Telomeres consist of DNA and associated proteins that function to protect chromosomes from breaks and other forms of damage. Another important element that must be present on every HAC is a functioning centromere that allows for the proper separation and assortment of chromosomes during cell division. As telomeres are located at the ends of chromosomes, centromeres are usually in the middle. Both regions contain repetitive DNA, or sequences that are repeated throughout the genome. These sequences are important regulatory regions and play a role in maintaining the integrity of the chromosome.

In contrast to normal chromosomes, HACs contain far less extraneous non-functional genetic material. Accordingly, the use of HACs gives researchers the ability to limit the genetic complexity by reducing the number of genes present on a chromosome. In addition to being able to control which genes are present, the construction of HACs offers researchers an opportunity to study less complex systems of gene interaction that are similar to natural chromosomes.

HACs are capable of self-assembly. When the required and proper genetic elements are introduced into cells, (e.g., telomeres, centromeric DNA, gene carrying DNA, etc.), smaller versions of chromosomes (microchromosomes) can be created. These resulting microchromosomes are what makes up a HACs.

In gene therapy, HACs have the ability to function as additional accessory chromosomes to natural chromosomes. The ability to construct artificial chromosomes that can remain stable through the cellular division offers an alternative to the use of viruses (viral vectors) to introduce therapeutic genes into natural chromosomes. The key to this design in terms of stability relied on the application of centromeres, which were shown to be critical for dividing the chromosome when the cell replicates its DNA and divides into two new cells. Additionally, the construction of a HAC carrying desired therapeutic genes eliminates potential damage to natural chromosomes often associated with the introduction of genes by viruses.