title: Human artificial chromosomes for gene delivery and the development of animal models.
abstract: Random integration of conventional gene delivery vectors such as viruses, plasmids, P1 phage-derived artificial chromosomes, bacterial artificial chromosomes and yeast artificial chromosomes can be associated with transgene silencing. Furthermore, integrated viral sequences can activate oncogenes adjacent to the insertion site resulting in cancer. Various human artificial chromosomes (HACs) exhibit several potential characteristics desired for an ideal gene delivery vector, including stable episomal maintenance and the capacity to carry large genomic loci with their regulatory elements, thus allowing the physiological regulation of the introduced gene in a manner similar to that of native chromosomes. HACs have been generated mainly using either a "top-down approach" (engineered chromosomes), or a "bottom-up approach" (de novo artificial chromosomes). The recent emergence of stem cell-based tissue engineering has opened up new avenues for gene and cell therapies. This review describes the lessons learned and prospects identified mainly from studies in the construction of HACs and HAC-mediated gene expression systems in cultured cells, as well as in animals.
authors.affiliation: Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kazuki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
mesh_terms: D000818:Animals; D002460:Cell Line; D022222:Chromosomes, Artificial, Human / Q000235:genetics*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D056426:Genetic Loci; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D019076:Transgenes