Retrovirus vector production and transduction: modulation by the cell cycle.
In this study, the cell cycle modulation of retrovirus vector production and transduction was analysed. Retrovirus vector expression was found to be similar in all phases of the cell cycle and, in contrast to some other virus promoters shown previously to be upregulated by G(2)/M arrest, Moloney murine leukaemia virus LTR-driven expression was upregulated neither by G(2)/M growth arrest nor by G(1)/S growth arrest. In contrast, cultures enriched for S phase cells produced more infectious virions, apparently by modulation of stages consequent to provirus expression. In terms of retrovirus transduction, limitations appear to be slow progression through the cell cycle and short half-life of the virus. Synchronization of cells prior to mitosis can increase transduction efficiency. Cell cycle modulation can be used to modify retrovirus vector production and transduction and can allow short transduction periods.
School of Physiology and Pharmacology, The University of New South Wales, Sydney, NSW 2052, Australia and Children's Cancer Institute, Randwick, Sydney, NSW 2031, Australia.|Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
Alla
A
Dolnikov
Johnson and Johnson Research Laboratories, The Australian Technology Park, Eveleigh, NSW 1430, Australia.|Department of Biotechnology, The University of New South Wales, Sydney, NSW 2053, Australia.
Simon
S
Wotherspoon
School of Physiology and Pharmacology, The University of New South Wales, Sydney, NSW 2052, Australia and Children's Cancer Institute, Randwick, Sydney, NSW 2031, Australia.|Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
Michelle
M
Millington
Department of Medicine, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.|School of Physiology and Pharmacology, The University of New South Wales, Sydney, NSW 2052, Australia and Children's Cancer Institute, Randwick, Sydney, NSW 2031, Australia.|Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.|Johnson and Johnson Research Laboratories, The Australian Technology Park, Eveleigh, NSW 1430, Australia.
Geoff
G
Symonds
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D016195:G2 Phase; D005822:Genetic Vectors; D006801:Humans; D008938:Mitosis; D012190:Retroviridae / Q000235:genetics* / Q000254:growth & development*; D014161:Transduction, Genetic; D014776:Virus Cultivation; D016662:Virus Integration