Human artificial chromosomes

Artificial chromosomes (Chapter 9) have been constructed as a means of better understanding the functional significance of many structural features of eukaryotic chromosomes. A reasonably stable artificial linear chromosome requires only three components a centromere, telomeres at each end, and sequences that allow the initiation of DNA replication. Yeast artificial chromosomes (YACs see Fig. 9-8) have been developed as a research tool in biotechnology. Similarly, human artificial chromosomes (HACs) are being developed for the treatment of genetic diseases by somatic gene therapy. 

As mentioned in Section B, 1, human centromeres are rich in the repetitive a-satellite DNA. By joining a-satellite DNA-containing fragments of the X-chro-mosome to cloned telomeric DNA, human minichromosomes have been created.488 These have been developed into human artificial chromosomes,489 which may be practical vehicles for gene transfer in human therapy. 

Attempts to obviate the limitations of retrovirus vectors include the use of alternative virus vectors such as adeno-associated viruses (now used in approximately 20 percent of clinical trials) and lenteviruses, as well as nonviral vectors such as plasmid-based vectors, either alone, in combination with liposomes, or linked to a ligand. Other, more theoretical, strategies proposed involve the creation of a human artificial chromosome. In this case, a 25th chromosome containing suites of genes would, it is hoped, be introduced into the nucleus of a target cell. 

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The immunoglobulin k locus of the mouse in comparison to the human k locus Use of yeast artificial chromosomes (YACs) for transgenesis... 

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