PMID: 8610167Apr 2, 1996Paper

Successful expression of human factor IX following repeat administration of adenoviral vector in mice

Proceedings of the National Academy of Sciences of the United States of America
J WalterK A High

Abstract

Adenoviral vectors can direct high-level expression of a transgene, but, due to a host immune response to adenoviral antigens, expression is of limited duration, and repetitive administration has generally been unsuccessful. Exposure to foreign proteins beginning in the neonatal period may alter or ablate the immune response. We injected adult and neonatal (immunocompetent) CD-1 mice intravenously with an adenoviral vector expressing human blood coagulation factor IX. In both groups of mice, expression of human factor IX persisted for 12-16 weeks. However, in mice initially injected as adults, repeat administration of the vector resulted in no detectable expression of the transgene, whereas in mice initially injected in the neonatal period, repeat administration resulted in high-level expression of human factor IX. We show that animals that fail to express the transgene on repeat administration have developed high-titer neutralizing antibodies to adenovirus, whereas those that do express factor IX have not. This experimental model suggests that newborn mice can be tolerized to adenoviral vectors and demonstrates that at least one repeat injection of the adenoviral vector is possible; the model will be useful in elucidating the ...Continue Reading

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Citations

Feb 24, 2001·The Journal of Gene Medicine·L GraveM Mehtali
May 15, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y IlanJ R Chowdhury
Oct 2, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yongping YueDongsheng Duan
Apr 5, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anton P McCaffreyMark A Kay
Nov 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jonathan D FinnKatherine A High
Jun 2, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jae-Hyung JangLonnie D Shea
Sep 20, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Leszek LisowskiMark A Kay
Apr 19, 2011·Nature Reviews. Genetics·Federico Mingozzi, Katherine A High
Oct 24, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samuel L MurphyKatherine High
Feb 15, 2002·British Journal of Haematology·K J Pasi
Apr 25, 2001·Clinical and Laboratory Haematology·G EmilienC Casimir
Jan 10, 2002·Human Gene Therapy·Jay N LozierRichard A Morgan
Oct 25, 2002·Human Gene Therapy·Paul WaszakChristophe Delacourt
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Nov 2, 2005·Human Gene Therapy·Emmanuelle FleurenceChristophe Delacourt
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May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·R W HerzogK A High
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Feb 16, 2008·British Journal of Haematology·Samuel L Murphy, Katherine A High
Aug 18, 2005·Biochemical and Biophysical Research Communications·N KuwadaE R B McCabe
May 25, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anton P McCaffreyMark A Kay

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