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A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA
Open accessAbstract
We describe the use of lentiviral vectors expressing small interfering RNAs (siRNAs) to knock down the expression of specific genes in vitro and in vivo . A lentiviral vector capable of generating siRNA specific for GFP after transduction of 293T-GFP cell lines showed no GFP fluorescence. Furthermore, no GFP-specific RNA could be detected. When eggs from GFP-positive transgenic mice were transduced with lentivirus-expressing siGFP virus, reduced fluorescence could be seen in blastocysts. More interestingly, pups from F 1 progeny, which expressed siGFP, showed considerably diminished fluorescence and decreased GFP. We propose that an approach of combining transgenesis by lentiviral vectors expressing siRNAs can be used successfully to generate a large number of mice in which the expression of a specific gene(s) can be down-regulated substantially. We believe that this approach of generating “knockdown” mice will aid in functional genomics.
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In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Self-citationA Third-Generation Lentivirus Vector with a Conditional Packaging System
Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341
‘Green mice’ as a source of ubiquitous green cells
Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T., & Nishimune, Y. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00313-x · Cited by 2,581
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Cited by
MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review
Iorio, M. V., & Croce, C. M. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100209 · Cited by 1,739
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969
In vivo imaging of siRNA delivery and silencing in tumors
Medarova, Z., Pham, W., Farrar, C., Petkova, V., & Moore, A. (2007) · Nature Medicine · doi:10.1038/nm1486 · Cited by 697
Heldt, S. A., Stanek, L., Chhatwal, J. P., & Ressler, K. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001957 · Cited by 684
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes
Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703778104 · Cited by 658
Metadata
- Authors
- Tiscornia, G., Singer, O., Ikawa, M., & Verma, I. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-01-27
- Volume
- 100
- Issue
- 4
- Pages
- 1844-1848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2130083086
- Cited by
- 540
- References
- 3
- FWCI
- 26.06
- Type
- journal article
- Language
- en
- Open access
- bronze
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