Functional expression of the single subunit NADH dehydrogenase in mitochondria in vivo: a potential therapy for complex I deficiencies

Human Gene Therapy
Byoung Boo SeoAkemi Matsuno-Yagi

Abstract

It has been reported that defects of mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) are involved in many human diseases (such as encephalomyopathies and sporadic Parkinson's disease). However, no effective remedies have been established for complex I deficiencies. We have adopted a gene therapy approach utilizing the NDI1 gene that codes for the single subunit NADH dehydrogenase of Saccharomyces cerevisiae (Ndi1). Our earlier experiments show that the Ndi1 protein can replace or supplement the functionality of complex I in various cultured cells. For this approach to be useful, it is important to demonstrate in vivo that the mature protein is correctly placed in mitochondria. In this study, we have attempted in vivo expression of the NDI1 gene in skeletal muscles and brains (substantia nigra and striatum) of rodents. In all tissues tested, the Ndi1 protein was identified in the injected area by immunohistochemical staining at 1-2 weeks after the injection. Sustained expression was observed for at least 7 months. Double-staining of the sections using antibodies against Ndi1 and F(1)-ATPase revealed that the expressed Ndi1 protein was predominantly localized to mitochondria. In addition, the tissue cel...Continue Reading

References

Jan 1, 1994·Annual Review of Nutrition·J M Shoffner, D C Wallace
Dec 2, 2000·Nature Neuroscience·R BetarbetJ T Greenamyre
Nov 15, 2001·The Journal of Biological Chemistry·Amy B Manning-BogDonato A Di Monte
Jan 12, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Brian K KasparDaniel A Peterson
Jan 19, 2002·IUBMB Life·J T GreenamyreA V Panov
Jul 4, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cathryn MahBarry J Byrne
Sep 17, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Byoung Boo SeoAkemi Matsuno-Yagi
Oct 29, 2002·Annals of Neurology·John GuyAlfred S Lewin
Mar 20, 2003·Molecular & Cellular Proteomics : MCP·Joe CarrollJohn E Walker
Apr 16, 2003·Methods : a Companion to Methods in Enzymology·Jaime GrutzendlerWen-Biao Gan
Nov 1, 2003·Science·Ted M Dawson, Valina L Dawson
Mar 6, 2004·Expert Review of Molecular Diagnostics·Rolf J R J JanssenJan A M Smeitink

❮ Previous
Next ❯

Citations

Dec 21, 2006·Pharmaceutical Research·Gerard G M D'SouzaVolkmar Weissig
Dec 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Leslie I GradBernard D Lemire
Jan 19, 2010·Annual Review of Pathology·Douglas C WallaceVincent Procaccio
Oct 13, 2011·PloS One·Mathieu MarellaTakao Yagi
Oct 12, 2012·Environmental and Molecular Mutagenesis·Yu-Hung SuWenya Huang
May 13, 2005·Mechanisms of Ageing and Development·Marina JendrachJürgen Bereiter-Hahn
May 12, 2007·Bioscience Reports·Julie L GardnerRobert W Taylor
Nov 26, 2008·Biochimica Et Biophysica Acta·Salvatore Dimauro, Pierre Rustin
Apr 4, 2006·Biochimica Et Biophysica Acta·Takao YagiAkemi Matsuno-Yagi
Oct 14, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jason R RichardsonGary W Miller
Jan 4, 2007·The Journal of Biological Chemistry·Tetsuo YamashitaTakao Yagi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

AAV-based Gene Therapy

Adeno-associated virus (AAV)-based gene therapy is a biological vector that is being researched to be used as a potential therapeutic option. This gene therapy is designed to insert fragments of DNA into targeted cells to help treat diseases, such as hemophilia a. Discover the latest research on AAV-based gene therapy here.

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.