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Citations to this article

Oral tolerization to adenoviral antigens permits long-term gene expression using recombinant adenoviral vectors.
Y Ilan, … , N R Chowdhury, J R Chowdhury
Y Ilan, … , N R Chowdhury, J R Chowdhury
Published March 1, 1997
Citation Information: J Clin Invest. 1997;99(5):1098-1106. https://doi.org/10.1172/JCI119238.
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Research Article Article has an altmetric score of 3

Oral tolerization to adenoviral antigens permits long-term gene expression using recombinant adenoviral vectors.

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Abstract

Recombinant adenoviruses (Ads) efficiently transfer foreign genes into hepatocytes in vivo, but the duration of transgene expression is limited by the host immune response which precludes gene expression upon readministration of the virus. To test if this immune response can be abrogated by oral tolerization, we instilled protein extracts of a recombinant adenovirus type-5 via gastroduodenostomy tubes into bilirubin-UDP-glucuronosyltransferase-1 (BUGT1)-deficient jaundiced Gunn rats. Control rats received BSA. Subsequent intravenous injection 5 x 10(9) pfu of a recombinant adenovirus-expressing human BUGT1 (Ad-hBUGT1) resulted in hepatic expression of human BUGT1 (hBUGT1) with reduction of serum bilirubin levels by 70%. After 2 mo serum bilirubin increased gradually. In orally tolerized rats, but not in controls, a second dose of the virus on day 98 markedly reduced serum bilirubin again. In the tolerized rats, the development of antiadenoviral neutralizing antibodies and cytotoxic lymphocytes were markedly inhibited, and transplantation of their splenocytes into naive Gunn rats adoptively transferred the tolerance, indicating a role for regulatory cells. Lymphocytes from the tolerized rats hyperexpressed TGFbeta1, IL2, and IL4 upon exposure to viral antigens, whereas IFNgamma expression became undetectable. Thus, oral tolerization with adenoviral antigens permits long-term gene expression by repeated injections of recombinant adenoviruses.

Authors

Y Ilan, R Prakash, A Davidson, . Jona, G Droguett, M S Horwitz, N R Chowdhury, J R Chowdhury

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Total citations by year

Year: 2020 2015 2013 2011 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1994 1992 1983 Total
Citations: 2 1 2 2 1 2 1 3 8 8 13 14 10 13 14 16 4 1 1 1 117
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Citations to this article in year 2009 (1)

Title and authors Publication Year
GENE THERAPY FOR THE TREATMENT OF PITUITARY TUMORS
SS Rodriguez, MG Castro, OA Brown, RG Goya, GM Console
Expert Review of Endocrinology & Metabolism 2009

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Referenced in 6 patents
21 readers on Mendeley
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