Human Artificial Chromosomes

Chromosomes are located in an organelle called the nucleus that is found in almost every cell. Chromosomes contain DNA tightly packaged in order to conserve space. Chromosomes are unwound during gene expression, which produces proteins. Recently human artificial chromosomes (HAC) have come into the forefront of gene therapy. Gene therapy—the transfer of corrected gene to cells with an endogenously defective gene—has had many setbacks toward becoming a medically routine therapeutic approach. Gene transfer often has a low efficiency targets, limited specific cell type targets. In addition, once transferred, gene expression is poorly regulated and this leads to a reduced therapeutic value.

Many currently used vectors can only package small genes, while HACs lack size restrictions. In fact, these constructs might be useful in delivering large genes, such as the genes that cause muscular dystrophy or cystic fibrosis. It will also be applicable to delivery of multiple genes such as anticancer genes. Using HACs as vectors for transferring genes might also lead to reducing life threatening immune-related complications observed with other vectors, and improve regulation of gene expression due to its very similar construction, modeled after normal human chromosomes. Preliminary studies also demonstrate HACs to be more stable.

In addition to being structurally similar to normal chromosomes, HAC can be designed to carry less non-gene related DNA than other vectors for gene therapy. Because the type of genetic material used to construct human artificial chromosomes can be regulated similarly compared to how normal human chromosomes are regulated, geneticists argue that HACs will take on an increasingly important role in gene therapy. The ability to regulate gene expression from artificial chromosomes allows scientists and clinicians the ability to introduce genes that ultimately produce specific therapeutic proteins needed to treat specific genetic diseases in a more controlled way.