Journal of Bioequivalence & Bioavailability

Human artifi cial chromosome (HAC) vector with a conditional centromere for correction of genetic defi ciencies in human cells

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Natalay Kouprina

Scientific Tracks Abstracts: JBB

Abstract:

H uman artifi cial chromosome HAC-based vectors off er a promising system for delivery and expression of full-length human genes of any size. HACs avoid the limited cloning capacity, lack of copy number control and insertional mutagenesis due to integration into host chromosomes that plague viral vectors. We previously described a synthetic HAC that can be easily eliminated from cell populations by inactivation of its conditional kinetochore. Th is HAC has a unique gene acceptor site. Here, we demonstrate the utility of the synthetic HAC for delivery of full-length genes and correction of genetic defi ciencies in human cells. We also show that phenotypes arising from stable gene expression from the HAC can be reversed when cells are ?cured? of the HAC by inactivating its kinetochore in proliferating cell populations. Our results demonstrate the benefi t of the combining TAR gene cloning technology with the HAC system for gene transfer and expression studies.