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TY - JOUR AU - Rubinson, Douglas A AU - Dillon, Christopher P AU - Kwiatkowski, Adam V AU - Sievers, Claudia AU - Yang, Lili AU - Kopinja, Johnny AU - Rooney, Dina L AU - Zhang, Mingdi AU - Ihrig, Melanie M AU - McManus, Michael T AU - Gertler, Frank B AU - Scott, Martin L AU - Van Parijs, Luk PY - 2003 DA - 2003/03/01 TI - A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference JO - Nature Genetics SP - 401 EP - 406 VL - 33 IS - 3 AB - RNA interference (RNAi) has recently emerged as a specific and efficient method to silence gene expression in mammalian cells either by transfection of short interfering RNAs (siRNAs; ref. 1) or, more recently, by transcription of short hairpin RNAs (shRNAs) from expression vectors and retroviruses2,3,4,5,6,7,8,9,10. But the resistance of important cell types to transduction by these approaches, both in vitro and in vivo11, has limited the use of RNAi. Here we describe a lentiviral system for delivery of shRNAs into cycling and non-cycling mammalian cells, stem cells, zygotes and their differentiated progeny. We show that lentivirus-delivered shRNAs are capable of specific, highly stable and functional silencing of gene expression in a variety of cell types and also in transgenic mice. Our lentiviral vectors should permit rapid and efficient analysis of gene function in primary human and animal cells and tissues and generation of animals that show reduced expression of specific genes. They may also provide new approaches for gene therapy. SN - 1546-1718 UR - https://doi.org/10.1038/ng1117 DO - 10.1038/ng1117 ID - Rubinson2003 ER -