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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Verma, Inder M. Pfeifer, Alexander Dayn, Yelena Ikawa, Masahito |
| Description | Author Affiliation: Pfeifer A ( The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.); |
| Abstract | The introduction of foreign genes into early mouse embryos and embryonic stem (ES) cells is invaluable for the analysis of gene function and regulation in the living animal. The use of vectors derived from retroviruses as gene transfer vehicles in this setting has had limited success because of silencing of transgene expression. Here, we show that vectors derived from lentiviruses, which are complex retroviruses, can efficiently deliver genes to murine ES cells and that transgene expression is stable during proliferation of undifferentiated ES cells. The transgene is expressed during differentiation of ES cells in vitro (embryoid bodies) and in vivo (teratomas). Transfer of lentivector-transduced ES cells into blastocysts resulted in chimeric animals that expressed the transgene in multiple tissues. Embryos derived from crossings of chimeric mice expressed the transgene, indicating successful germ-line transmission. Infection of murine preimplantation embryos at morula stage with lentiviral vectors resulted in stable transduction and expression of the transgene in mouse embryos and in newborn mice. Finally, human ES cells were transduced by lentiviral vectors and expressed the transgene over several passages. Thus, lentiviral vectors represent a significant improvement over oncoretroviral vectors used previously for gene transfer into murine ES cells and preimplantation embryos. Ability to transfer foreign genes into human ES cells has potential relevance for the development of gene and cell-based therapies. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Lentivirus Genetics Animals Blastocyst Metabolism Blotting, Southern Cell Differentiation Cell Division Cell Lineage Embryo, Mammalian Cytology Gene Transfer Techniques Genetic Therapy Green Fluorescent Proteins Luminescent Proteins Mice Mice, Inbred BALB C Mice, Inbred C57BL Microscopy, Fluorescence Models, Genetic Promoter Regions, Genetic Stem Cells Time Factors Transgenes Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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