Human artificial chromosomes (HAC) are synthetic chromosomes that are structurally similar to normal chromosomes that, in addition to being artificially created, carry less non-gene related DNA. Because the type of genetic material used to construct human artificial chromosomes can be carefully controlled, geneticists argue that HACs will take on an increasingly important role in gene therapy. The ability to control the types of genes present on chromosomes allows scientists and clinicians the ability to introduce genes that produce specific therapeutic proteins needed to treat a specific genetic diseases.
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 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.
In contrast to normal chromosomes, human artificial chromosomes contain far less extraneous non-functional genetic material (genomic material). Accordingly, the use of human artificial chromosomes allows researchers the ability to limit 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 human artificial chromosomes offers researchers an opportunity to study much simpler and less complex systems of gene interaction than are found in natural chromosomes.
Human artificial chromosomes 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) form. The resulting microchromosomes are then termed human artificial chromosomes
In gene therapy, human artificial chromosomes have the ability to function as additional accessory chromosomes to natural chromosomes. The ability to construct artificial chromosomes that can remain stable through the cell division process offers an alternative to the use of viruses (viral vectors) to introduce therapeutic genes into natural chromosomes. The construction of a HAC carrying desired therapeutic genes eliminates potential damage to natural chromosomes often associated with the introduction of genes by viruses. In addition, HACs offer the additional advantage of not inducing unwanted immune responses often associated with viral vectors.
Early attempts to create HACs failed because such artificial chromosomes lacked fully functional centromeres. Without a functional centromere, early HACs would not properly divide during cell division and thus, could not remain intact or stable for more than a few cell generations. In 1997, research scientists at Case Western Reserve University and Athersys, Inc., (a private company that conducts research into the development of therapeutic and diagnostic products, including research into the stability of chromosome structure and function) announced the creation of the first stable HAC. Functional HAC centromeres were constructed from alpha satellite DNA, a type of highly repetitive DNA found in and surrounding normal chromosome centromeres.
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