Constant and steady transgene expression of interferon-γ by optimization of plasmid construct for safe and effective interferon-γ gene therapy

The Journal of Gene Medicine
Mitsuru AndoYoshinobu Takakura

Abstract

Hydrodynamic injection of pmCMV(enh) -hEF-1(prom) -muIFN-γ, a plasmid DNA (pDNA) expressing murine interferon (IFN)-γ with a murine cytomegalovirus (mCMV) enhancer and a human elongation factor (EF)-1 promoter, has been proven effective for the treatment of cancer and atopic dermatitis in mice. However, the initial peak of IFN-γ soon after injection was quite high compared to the steady level for subsequent periods, which could cause unwanted adverse effects. Therefore, in the present study, aiming to optimize the efficacy/side-effect ratio of IFN-γ gene transfer, we have developed plasmid vectors encoding murine IFN-γ under the control of different combinations of promoter and enhancer sequences. The promoter and enhancer sequence of pmCMV(enh) -hEF-1(prom) -huIFN-γ, a prototype plasmid expressing human IFN-γ, was replaced or deleted to obtain various pDNAs. To assess the transgene expression profile, each pDNA was delivered to mice by hydrodynamic injection and the serum IFN-γ concentration was measured periodically. On the basis of the results obtained, murine IFN-γ expressing pDNAs were constructed and the body weight change was monitored as an indicator of adverse effects. The prototype pmCMV(enh) -hEF-1(prom) -huIFN-γ sho...Continue Reading

References

Feb 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J R QuesadaJ U Gutterman
Jan 1, 1985·Cancer Immunology, Immunotherapy : CII·K A FoonR B Herberman
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·B P ZambrowiczP Soriano
Jul 22, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·C N EllisK D Cooper
Mar 1, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael FreseRalf Bartenschlager
Oct 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Priscilla L YangFrancis V Chisari
Nov 20, 2004·Clinical and Experimental Dermatology·A Grassegger, R Höpfl
May 26, 2005·Journal of Hepatology·Alejandro SozaJay H Hoofnagle
May 24, 2006·The Journal of Gene Medicine·Vladimir G BudkerJon A Wolff
May 26, 2006·The Journal of Gene Medicine·Magdolna G SebestyénJon A Wolff
Mar 21, 2007·International Journal of Cancer. Journal International Du Cancer·Hiroki KawanoYoshinobu Takakura
Feb 7, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhi-Ying ChenMark A Kay
Apr 29, 2008·Nature Biotechnology·Stephen C HydeDeborah R Gill
Jan 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kayoko HattoriYoshinobu Takakura

❮ Previous
Next ❯

Citations

Nov 28, 2013·Human Gene Therapy. Clinical Development·Yuki TakahashiYoshinobu Takakura
Sep 22, 2012·Journal of Drug Targeting·Kanitta WatcharanurakYoshinobu Takakura
Sep 4, 2018·Biological & Pharmaceutical Bulletin·Tetsuya SuzukiHiroyuki Kamiya
Oct 2, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuki Takahashi
Dec 5, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Mitsuru AndoYoshinobu Takakura
Mar 13, 2014·The Journal of Biological Chemistry·Pavel KopachSergei P Atamas
Jun 23, 2021·Nature Reviews. Immunology·Angela M GocherDario A A Vignali

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.

Related Papers

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Mitsuru AndoYoshinobu Takakura
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Makiya NishikawaYoshinobu Takakura
Genesis : the Journal of Genetics and Development
Richard PossematoLaurie Jackson-Grusby
© 2022 Meta ULC. All rights reserved