Human cytomegalovirus plasmid-based amplicon vector system for gene therapy.
We have constructed and evaluated the utility of a helper-dependent virus vector system that is derived from Human Cytomegalovirus (HCMV). This vector is based on the herpes simplex virus (HSV) amplicon system and contains the HCMV orthologs of the two cis-acting functions required for replication and packaging of HSV genomes, the complex HCMV viral DNA replication origin (oriLyt), and the cleavage packaging signal (the a sequence). The HCMV amplicon vector replicated independently and was packaged into infectious virions in the presence of helper virus. This vector is capable of delivering and expressing foreign genes in infected cells including progenitor cells such as human CD34+ cells. Packaged defective viral genomes were passaged serially in fibroblasts and could be detected at passage 3; however, the copy number appeared to diminish upon serial passage. The HCMV amplicon offers an alternative vector strategy useful for gene(s) delivery to cells of the hematopoietic lineage.
Mahmood
Kutubuddin
K
MedImmune Vaccines Inc,, 297 North Bernardo Avenue, Mountain View, CA 94043 USA. spaeter@medimmune.com.
Prichard
Mark N
MN
Duke
Gregory M
GM
Kemble
George W
GW
Spaete
Richard R
RR