{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:21:50Z","timestamp":1772137310241,"version":"3.50.1"},"reference-count":19,"publisher":"Proceedings of the National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,2,18]]},"abstract":"<jats:p>\n                    We describe the use of lentiviral vectors expressing small interfering RNAs (siRNAs) to knock down the expression of specific genes\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . 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\n                    <jats:sub>1<\/jats:sub>\n                    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 \u201cknockdown\u201d mice will aid in functional genomics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0437912100","type":"journal-article","created":{"date-parts":[[2003,2,18]],"date-time":"2003-02-18T15:04:50Z","timestamp":1045580690000},"page":"1844-1848","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":426,"title":["A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA"],"prefix":"10.1073","volume":"100","author":[{"given":"Gustavo","family":"Tiscornia","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037"}]},{"given":"Oded","family":"Singer","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037"}]},{"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037"}]},{"given":"Inder M.","family":"Verma","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037"}]}],"member":"341","published-online":{"date-parts":[[2003,1,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/418244a"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)41914-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35078107"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068999"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/418038a"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt739"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5259.263"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11382"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8463-8471.1998"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220399597"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-314"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251682798"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","unstructured":"Sui G. Soohoo C. Affar el B. Gay F. Shi Y. & Forrester W. C. (2002) Proc. Natl. Acad. Sci. USA 99 5515\u20135520.","DOI":"10.1073\/pnas.082117599"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.092143499"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.981002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067081"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00313-X"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/87979"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00481-9"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0437912100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:20:58Z","timestamp":1649773258000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0437912100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,27]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,2,18]]}},"alternative-id":["10.1073\/pnas.0437912100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0437912100","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1013219.189614","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1,27]]},"assertion":[{"value":"2002-12-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}