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An XMRV Tool Box: Expression Plasmids, Genes, and Proteins for All Components of the Xenotropic Murine Leukemia Virus-Related Vi

Posted Aug 22 2010 5:00pm

Description of Invention:
The xenotropic murine leukemia virus-related virus (XMRV) has been implicated as a possible causative agent of prostate cancer and chronic fatigue syndrome (CFS). Scientists at the National Institutes of Health (NIH) and Science Applications International Corporation in Frederick, MD (SAIC-Frederick) have developed sixty four (64) protein expression plasmids for components of XMRV. One or more XMRV proteins made available through these expression plasmids could have clinical relevance to diagnosing or treating human disease. The work to develop this technology was performed in the Protein Expression Laboratory at SAIC-Frederick in collaboration with expert retrovirologists from the National Cancer Institute's Frederick, MD campus, a site well-positioned to develop these expression plasmids from initial cloning to final validations. The development of these XMRV tools is expected to save researchers months in laboratory production time and thousands of dollars in labor costs.

The XMRV strain utilized to generate these expression plasmids is a reference strain isolated from a human patient. Each expression plasmid encodes one of the ten proteins that comprise the XMRV retrovirus (matrix, p12, capsid, nucleocapsid, protease, reverse transcriptase, integrase, surface, transmembrane, and envelope). Nine of the ten XMRV proteins expressed by these clones have been successfully purified in large quantities using scale-up processes. The expression vectors were generated utilizing the Gateway® cloning system and consist of Gateway® entry clones, bacterial (Escherichia coli) expression clones, baculovirus expression clones, and mammalian expression clones. Expression of the appropriate XMRV protein from its corresponding expression clone has been confirmed. The entry clones have been validated for Gateway® subcloning and the baculovirus clones have been validated for baculovirus production and can be transposed into baculoviral genomes. The plasmids have been fully mapped and sequenced and contain one or more elements to facilitate laboratory use, such as antibiotic resistance genes, specialized promoter sequences, maltose-binding protein and His tags, TEV protease sites, Kozak-ATG sequences, signal peptides, and other elements.

Applications:
  • Research tool whose large-scale production capability can be utilized to develop serological assays for detecting XMRV and other retroviruses to possibly establish these viruses as causative agents for CFS, prostate cancer, and other diseases with unknown origins
  • Collection of research tools that could be utilized to develop a complete set of diagnostic assays for detecting each of these XMRV proteins in patient samples
  • Research tool to serve as a platform for developing therapeutic moieties, such as neutralizing antibodies and other biologics, for treating prostate cancer, chronic fatigue syndrome, and any other disease where XMRV is later identified as the causative agent
  • A logical starting point for generating clinical-grade XMRV constructs for use in clinical vaccine, immunotherapy, and gene therapy studies


Advantages:
  • First complete set of plasmids available for the expression of each XMRV protein individually: Researchers looking to study XMRV can save months of time and thousands of dollars by using this set of XMRV tools. The plasmids have been fully-mapped and validated for protein expression. This plasmid portfolio offers a variety of vectors for expressing these XMRV proteins including Gateway® entry clones, bacterial vectors, baculoviral vectors, and mammalian expression systems.
  • Clones were developed from an XMRV isolate taken from a patient with a confirmed XMRV infection: The proteins produced by these expression plasmids are anticipated to have direct clinical applicability to human XMRV diseases.
  • Launching pad for any commercial entity desiring to develop diagnostics or therapeutics for XMRV: This technology is likely to give companies in the prostate cancer arena or the emerging chronic fatigue syndrome market a competitive advantage for developing anti-XMRV products faster than competitors. The molecular targets needed as a starting point for therapeutic development are provided by this technology.


Inventors:
Dominic Esposito (NCI)
Alan R Rein (NCI)
James L Hartley (NCI)
Stuart F LeGrice (NCI)
William K Gillette (NCI)
Ralph F Hopkins (NCI)
Troy E Taylor (NCI)


Patent Status:
HHS, Reference No. E-155-2010/0

Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:
  1. VC Lombardi, et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 2009 Oct 23;326(5952):585-589. [ PubMed: 19815723 ]
  2. A Urisman, et al. Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog. 2006 Mar;2(3):e25. [ PubMed: 16609730 ]


Licensing Status:
Available for licensing under a Biological Materials License Agreement.


Portfolios:
Devices/Instrumentation
Devices/Instrumentation - Research Tools and Materials
Cancer
Cancer - Research Materials
Infectious Diseases
Infectious Diseases - Research Materials



For Licensing Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: bishse@mail.nih.gov
Phone: 301-435-5282
Fax: 301-402-0220


Ref No: 2153

Updated: 08/2010

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