Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Reexamination Certificate
1999-11-22
2001-09-04
Prouty, Rebecca E. (Department: 1652)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
C435S183000, C435S193000, C435S194000, C435S252300, C435S320100, C435S069100, C435S325000, C536S023200
Reexamination Certificate
active
06284507
ABSTRACT:
INTRODUCTION
Accumulation of mutations in the mitochondrial genome has been proposed as an important contributor to aging and degenerative diseases. In several cases human mitochondrial disorders have been shown to be caused by mutations or deletions of mitochondrial DNA.
There is evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage in the etiology of neurodegenerative diseases, including amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. It is likely that there is a complex interplay between these mechanisms. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age-dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases.
Mitochondria are dynamic organelles that undergo regulated fusion in many cell types. Analysis of serial sections from rodent skeletal muscle, lymphocytes, liver, spinal ganglion cells, and from the yeast
Saccharomyces cerevisiae
has shown that all the mitochondrial material of a cell can exist as a giant branched reticulum.
Specific protein mediators that act as biomechanical triggers and/or regulate specificity and timing of membrane fusion events have been identified in a wide variety of other cellular and subcellular contexts. The best characterized biomechanically acting fusogen is influenza virus hemagglutinin (HA) that mediates fusion of endocytosed viruses to cells. Regions resembling the HA fusion peptide exist in the ADAM family proteins, which are implicated in sperm/egg and myoblast fusion.
The identification of protein mediators of mitochondrial fusion and their possible role in maintenance of mitochondrial function and genomic integrity is of great interest for diagnosis, drug screening and potential therapeutic strategies, including targeted delivery of genes, proteins and molecules to existing mitochondria. If recombination between differently mutated mitochondrial DNA molecules allows restoration of a functional copy, the ability of mitochondria to fuse may play an important role in maintenance of mitochondrial genomes. Alternatively, fusion of mitochondria may allow complementation between two mutations in different genes in the mitochondrial genome, allowing restoration of mitochondrial function even in the absence of recombination.
Relevant literature
Larsson, N.-G., and D. A. Clayton. 1995. Molecular genetic aspects of human mitochondrial disorders. Annual Review of Genetics. 29:151-178.
Kawano, S., H. Takano, and T. Kuroiwa. 1995. Sexuality of mitochondria: fusion, recombination, and plasmids. Int. Rev. Cytol. 161:49-110.
SUMMARY OF THE INVENTION
Mitofusin genes and proteins are provided. As used herein, the term “mitofusin” indicates the Drosophila Fzo protein or any of its homologues from insects, other invertebrates, yeast, and vertebrates including mouse and humans. Motifusins are large predicted GTPases with a predicted trans-membranedomain, coiled-coil regions, and a C-terminal region showing a high pl characteristic of mitochondrial matrix proteins. The mitofusin Fzo is the first known protein mediator of mitochondrial fusion, and mediates developmentally regulated post-meiotic fusion of mitochondria in Drosophila spermatids.
REFERENCES:
patent: WO88/02372 (1988-04-01), None
patent: 95/06764 (1995-03-01), None
Bashkin, James K., et al., “Robozyme Mimics as Catalytic Antisense Reagents,”Applied Biochemistry and Biotechnology(1995) vol. 54:43-56.
Furth, Priscilla A., et al., “Gene Transfer Into Somatic Tissues By Jet Injection,”Analytical Biochemistry(1992) vol. 205:365-368.
Tang, De-chu, et al., “Genetic Immunization Is A Simple Method For Eliciting An Immune Response,”Nature(Mar. 12, 1992) vol. 356:152-154.
Wagner, Richard W., et al., “Potent and Selective Inhibition Of Gene Expression By An Antisense Heptanucleotide,”Nature Biotechnology(Jul., 1996) vol. 14:840-844.
The 1992 Sigma Catalog, Published by the Sigma chemical Company, Jan. 1, 1992, see p. 62, product No. A7627.
Fuller Margaret T.
Hales Karen G.
Bozicevic Field & Francis LLP
Prouty Rebecca E.
Rao Manjunath
Sherwood Pamela J.
The Board of Trustees of the Leland Stanford Junior University
LandOfFree
Mitofusin genes and their uses does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Mitofusin genes and their uses, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Mitofusin genes and their uses will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2463050