TY - JOUR
T1 - Development of mammalian artificial chromosomes for the treatment of genetic diseases
T2 - Sandhoff and Krabbe diseases
AU - Bunnell, Bruce A.
AU - Izadpanah, Reza
AU - Ledebur, Harry C.
AU - Perez, Carl F.
PY - 2005/2
Y1 - 2005/2
N2 - Mammalian artificial chromosomes (MACs) are being developed as alternatives to viral vectors for gene therapy applications, as they allow for the introduction of large payloads of genetic information in a non-integrating, autonomously replicating format. One class of MACs, the satellite DNA-based artificial chromosome expression vehicle (ACE), is uniquely suited for gene therapy applications, in that it can be generated de novo in cells, along with being easily purified and readily transferred into a variety of recipient cell lines and primary cells. To facilitate the rapid engineering of ACEs, the ACE System was developed, permitting the efficient and reproducible loading of pre-existing ACEs with DNA sequences and/or target gene(s). As a result, the ACE System and ACEs are unique and versatile platforms for ex vivo gene therapy strategies that circumvent and alleviate existing safety and delivery limitations surrounding conventional gene therapy vectors. This review will focus on the status of MAC technologies and, in particular, the application of the ACE System towards an ex vivo gene therapy treatment of lysosomal storage diseases, specifically Sandhoff (MIM #268800) and Krabbe (MIM #245200) diseases.
AB - Mammalian artificial chromosomes (MACs) are being developed as alternatives to viral vectors for gene therapy applications, as they allow for the introduction of large payloads of genetic information in a non-integrating, autonomously replicating format. One class of MACs, the satellite DNA-based artificial chromosome expression vehicle (ACE), is uniquely suited for gene therapy applications, in that it can be generated de novo in cells, along with being easily purified and readily transferred into a variety of recipient cell lines and primary cells. To facilitate the rapid engineering of ACEs, the ACE System was developed, permitting the efficient and reproducible loading of pre-existing ACEs with DNA sequences and/or target gene(s). As a result, the ACE System and ACEs are unique and versatile platforms for ex vivo gene therapy strategies that circumvent and alleviate existing safety and delivery limitations surrounding conventional gene therapy vectors. This review will focus on the status of MAC technologies and, in particular, the application of the ACE System towards an ex vivo gene therapy treatment of lysosomal storage diseases, specifically Sandhoff (MIM #268800) and Krabbe (MIM #245200) diseases.
KW - Artificial chromosomes
KW - Gene therapy
KW - Krabbe disease
KW - Lysosomal storage disease
KW - Sandhoff disease
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=15244354387&partnerID=8YFLogxK
U2 - 10.1517/14712598.5.2.195
DO - 10.1517/14712598.5.2.195
M3 - Review article
C2 - 15757381
AN - SCOPUS:15244354387
SN - 1471-2598
VL - 5
SP - 195
EP - 206
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 2
ER -