{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:19:38Z","timestamp":1792120778992,"version":"4.4.0"},"reference-count":44,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>\n                    Interferon gamma (IFN-\u03b3) is a 28\u2009kDa homodimeric cytokine that exhibits potent immunomodulatory, anti-proliferative, and antiviral properties. The protein is used to treat chronic granulomatous disease and malignant osteopetrosis, and it is under investigation as a treatment for a variety of cancer, fungal and viral diseases. IFN-\u03b3 has a short circulating half life\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , which necessitates frequent administration to patients. An unusual feature of IFN-\u03b3 is that the protein contains no native cysteines. To create a longer-acting and potentially more effective form of the protein, we introduced a cysteine residue into the IFN-\u03b3 coding sequence at amino acid position 103, which is located in a surface-exposed, non-helical region of the protein. The added cysteine residue served as the site for targeted modification of the protein with a cysteine-reactive polyethylene glycol (PEG) reagent. The recombinant protein was expressed in bacteria, purified and modified with 10, 20, and 40\u2009kDa maleimide PEGs. The purified, PEGylated proteins had\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    bioactivities comparable to IFN-\u03b3, as measured using an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    cell growth inhibition assay. The PEGylated proteins displayed 20- to 32-fold longer half lives than IFN-\u03b3 in rats, and they were significantly more effective than IFN-\u03b3 at inhibiting growth of a human tumor xenograft in athymic mice.\n                  <\/jats:p>","DOI":"10.1089\/jir.2013.0067","type":"journal-article","created":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T14:30:52Z","timestamp":1400509852000},"page":"759-768","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["PEGylation Improves the Pharmacokinetic Properties and Ability of Interferon Gamma to Inhibit Growth of a Human Tumor Xenograft in Athymic Mice"],"prefix":"10.1177","volume":"34","author":[{"given":"Christine M.","family":"Fam","sequence":"first","affiliation":[{"name":"Bolder BioTechnology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Chlipala","sequence":"additional","affiliation":[{"name":"Premier Laboratory LLC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George N.","family":"Cox","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary S.","family":"Rosendahl","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.01.005"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38587-3"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03094.x"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.05.027"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc070131q"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.1995.0028"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690491"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2833"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1902591"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.003035"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/295503a0"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.2.517"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(93)70026-P"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1033"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140070-00005"},{"key":"e_1_3_3_17_1","first-page":"177","volume-title":"PCR protocols: a guide to methods and applications","author":"Higuchi R","year":"1990","unstructured":"Higuchi R. 1990. Recombinant PCR. In: Innis MA, , Gelfand DH, , Sninsky JJ, , White TJ, eds. PCR protocols: a guide to methods and applications. San Diego, CA: Academic Press. pp 177\u2013183."},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.21.8247"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102213240801"},{"key":"e_1_3_3_20_1","first-page":"21","volume-title":"PCR protocols: a guide to methods and applications","author":"Kawasaki ES","year":"1990","unstructured":"Kawasaki ES. 1990. Amplification of RNA. In: Innis MA, , Gelfand DH, , Sninsky JJ, , White TJ, eds. PCR protocols: a guide to methods and applications. San Diego, CA: Academic Press. pp 21\u201327."},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506153322402"},{"key":"e_1_3_3_22_1","first-page":"2866","article-title":"Pharmacokinetics, single-dose tolerance, and biological activity of recombinant gamma-interferon in cancer patients","volume":"45","author":"Kurzrock R","year":"1985","unstructured":"Kurzrock R, , Rosenblum MG, , Sherwin SA, , Rios A, , Talpaz M, , Quesada JR, , Gutterman JU. 1985. Pharmacokinetics, single-dose tolerance, and biological activity of recombinant gamma-interferon in cancer patients. Cancer Res, 45:2866\u20132872.","journal-title":"Cancer Res"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2012.0148"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060993"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)33987-X"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/5.3.253"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-00009577-200607000-00005"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1705"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/161.5.992"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/420829"},{"issue":"3","key":"e_1_3_3_31_1","first-page":"S9-18","article-title":"The interferon receptors","volume":"24","author":"Pestka S","year":"1997","unstructured":"Pestka S. 1997. The interferon receptors. Semin Oncol, 24(3 Suppl 9):S9-18\u2013S9-40.","journal-title":"Semin Oncol"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(97)00009-9"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0829"},{"key":"e_1_3_3_34_1","first-page":"6790","article-title":"Natural human interferon-\u03b3","volume":"259","author":"Rinderknecht E","year":"1984","unstructured":"Rinderknecht E, , O'Conner BH, , Rodriguez H. 1984. Natural human interferon-\u03b3. Complete amino acid sequence and determination of sites of glycosylation. J Biol Chem, 259:6790\u20136797.","journal-title":"Complete amino acid sequence and determination of sites of glycosylation. J Biol Chem"},{"key":"e_1_3_3_35_1","first-page":"84","volume-title":"PCR protocols.","author":"Scharf SJ","year":"1990","unstructured":"Scharf SJ. 1990. Cloning with PCR. In: Innis MA, , Gelfand DH, , Sninsky JJ, , White TJ, eds. PCR protocols. San Diego, CA: Academic Press. pp 84\u201391."},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.17.5403"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00199301"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2002.6707"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/376230a0"},{"key":"e_1_3_3_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.149.3681.310"},{"key":"e_1_3_3_42_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.1053"},{"key":"e_1_3_3_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.134.3.1599"},{"key":"e_1_3_3_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0482"},{"key":"e_1_3_3_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012073432301"}],"container-title":["Journal of Interferon &amp; Cytokine Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jir.2013.0067","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jir.2013.0067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jir.2013.0067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:32:46Z","timestamp":1777455166000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jir.2013.0067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1089\/jir.2013.0067"],"URL":"https:\/\/doi.org\/10.1089\/jir.2013.0067","relation":{},"ISSN":["1079-9907","1557-7465"],"issn-type":[{"value":"1079-9907","type":"print"},{"value":"1557-7465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10]]}}}