Artificial Chromosome Vector


Artificial Chromosome Vector

Artificial chromosome vectors were developed by Professor Mitsuo Oshimura et al. in Tottori University Graduate School of Medicine by deleting gene regions unnecessary for the maintenance and division of chromosomes in the cell from human or mouse chromosomes. They are called HAC (human artificial chromosomes: artificial chromosomes derived from human chromosomes) vector or MAC (mouse artificial chromosomes: artificial chromosomes derived from mouse chromosomes) vector.

Since these artificial chromosome vectors inherit the properties of chromosomes, they have quite different properties from conventional plasmid/viral vectors.

In the method of constructing a stable gene expression cell line from a plasmid/viral vector or the like, it was necessary to insert the vector into which the desired foreign gene was integrated on the host chromosome in order to maintain it. During this, the vector was randomly inserted on the host chromosome, and the copy number was also variable, which made it difficult to control.

<Problems with the conventional method (plasmid/viral vector)>

  1. Restriction on DNA size to be transfected
  2. Destruction of host genes by insertion of foreign genes
  3. Changes in properties of cells, such as malignant transformation by insertion of foreign genes
  4. Difference in expression level between clones due to difference in insertion position and copy number
  5. Gene silencing by subculture

Since the artificial chromosome vector is retained independently of the host chromosome in the host cell line, the above problems can be solved.

Construction method of HAC (human artificial chromosome) vector


References:Y. Kazuki et al., Gene Therapy (2011) 18 384-393

Features of artificial chromosome vector

Artificial chromosome vectors have the following advantages compared to conventional vectors. Use for various applications is expected, such as the generation of a stable gene expression cell line, preparation of a transgenic animal, and construction of high protein producing cells.