{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:06:26Z","timestamp":1791295586735,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Some inborn errors of metabolism due to deficiencies of soluble lysosomal enzymes cause global neurodegenerative disease. Representative examples include the infantile and late infantile forms of the ceroid lipofuscinoses (CLN1 or CLN2 deficiency, respectively) and mucopolysaccharidoses type VII (MPS VII), a deficiency of \u03b2-glucuronidase. Treatment of the central nervous system component of these disorders will require widespread protein or enzyme replacement, either through dissemination of the protein or through dissemination of a gene encoding it. We hypothesize that transduction of brain microcapillary endothelium (BME) with recombinant viral vectors, with secretion of enzyme product basolaterally, could allow for widespread enzyme dissemination. To achieve this, viruses should be modified to target the BME. This requires (i) identification of a BME-resident target receptor, (ii) identification of motifs targeted to that molecule, (iii) the construction of modified viruses to allow for binding to the target receptor, and (iv) demonstrated transduction of receptor-expressing cells. In proof of principal experiments, we chose the human transferrin receptor (hTfR), a molecule found at high density on human BME. A nonamer phage display library was panned for motifs which could bind hTfR. Forty-three clones were sequenced, most of which contained an AKxxK\/R, KxKxPK\/R, or KxK motif. Ten peptides representative of the three motifs were cloned into the HI loop of adenovirus type 5 fiber. All motifs tested retained their ability to trimerize and bind transferrin receptor, and seven allowed for recombinant adenovirus production. Importantly, the fiber-modified viruses facilitated increased gene transfer (2- to 34-fold) to hTfR expressing cell lines and human brain microcapillary endothelia expressing high levels of endogenous receptor. Our data indicate that adenoviruses can be modified in the HI loop for expanded tropism to the hTfR.<\/jats:p>","DOI":"10.1128\/jvi.74.23.11359-11366.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:53Z","timestamp":1027763753000},"page":"11359-11366","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":141,"title":["Recombinant Human Adenovirus: Targeting to the Human Transferrin Receptor Improves Gene Transfer to Brain Microcapillary Endothelium"],"prefix":"10.1128","volume":"74","author":[{"given":"Haibin","family":"Xia","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Program in Gene Therapy, Departments of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Anderson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Program in Gene Therapy, Departments of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Mao","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Program in Gene Therapy, Departments of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly L.","family":"Davidson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Program in Gene Therapy, Departments of Internal Medicine1 and"},{"name":"<!--label omitted: 2-->Neurology,2 University of Iowa College of Medicine, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301197"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050015194"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950017635"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0178"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.28.16974"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.7.4805-4810.1996"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199505000-00012"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/8647"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1196-1574"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.11.9130-9136.1999"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.2.622-625.1988"},{"key":"e_1_3_2_13_2","first-page":"1491","article-title":"Characterization, receptor mapping and blood-brain barrier transcytosis of antibodies to the human transferrin receptor","volume":"278","author":"Friden P. M.","year":"1996","unstructured":"Friden P. M. Olson T. S. Obar R. Walus L. R. Putney S. D. Characterization, receptor mapping and blood-brain barrier transcytosis of antibodies to the human transferrin receptor.J. Pharmacol. Exp. Ther. 278 1996 1491 1498","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.16-2331"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300836"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300898"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.7071-7078.1996"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(74)90070-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050016238"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9829"},{"key":"e_1_3_2_22_2","first-page":"66","article-title":"Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo","volume":"259","author":"Pardridge W. M.","year":"1991","unstructured":"Pardridge W. M. Buciak J. L. Friden P. M. Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo.J. Pharmacol. Exp. Ther. 259 1991 66 70","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002620050294"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300941"},{"key":"e_1_3_2_25_2","unstructured":"Scriver\nC. R.\nThe metabolic basis of inherited disease.\n1989\nMcGraw-Hill Book Company\nNew York N.Y"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050015707"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2820"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7176"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700104"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.3424-3429.1999"},{"key":"e_1_3_2_31_2","first-page":"241","article-title":"The transferrin receptor","volume":"4","author":"Testa U.","year":"1993","unstructured":"Testa U. Pelosi E. Peschle C. The transferrin receptor.Crit. Rev. Oncog. 4 1993 241 276","journal-title":"Crit. Rev. Oncog."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300775"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002620050419"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1196-1570"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.6831-6838.1996"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8221-8229.1997"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2788"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.74.23.11359-11366.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.74.23.11359-11366.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T04:48:22Z","timestamp":1646455702000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.74.23.11359-11366.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12]]},"references-count":36,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2000,12]]}},"alternative-id":["10.1128\/JVI.74.23.11359-11366.2000"],"URL":"https:\/\/doi.org\/10.1128\/jvi.74.23.11359-11366.2000","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12]]},"assertion":[{"value":"2000-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}