Sequence X from Patent WO2011092199 (vaccination against XMRV?)

[Jemal]

A ton of sequences (27 so far) were posted to Genbank on 11 sep. This is an example:

LOCUS JA417529 32 bp DNA linear PAT 11-SEP-2011
DEFINITION Sequence 47 from Patent WO2011092199.
ACCESSION JA417529
VERSION JA417529.1 GI:346450266
KEYWORDS .
SOURCE synthetic construct
ORGANISM synthetic construct
other sequences; artificial sequences.
REFERENCE 1
AUTHORS HEIDMANN,T. and SCHLECHT-LOUF,G.
TITLE MUTATED XMRV ENV PROTEINS IN THE IMMUNOSUPPRESSIVE DOMAIN
JOURNAL Patent: WO 2011092199-A1 47 04-AUG-2011;
ROUSSY INST GUSTAVE [FR]; CENTRE NAT RECH SCIENT [FR]; UNIV PARIS
SUD XI [FR]; HEIDMANN THIERRY [FR]; SCHLECHT-LOUF GERALDINE [FR];
VIROXIS S A S [FR]
FEATURES Location/Qualifiers
source 1..32
/organism="synthetic construct"
/mol_type="other DNA"
/db_xref="taxon:32630"
/note="oligo nucleotide for PCR construction"
ORIGIN
1 gtatacgcgt ttaatgggaa ttggtaatat tc

http://www.ncbi.nlm.nih.gov/nuccore/JA417529.1

What's this then? I see "synthetic construct" so these are artificial?

This is the related patent:

The present invention relates to a mutated XMRV ENV protein in which the immunosuppressive domain of the wild type XMRV ENV protein presents at least one mutation, said immunosuppressive domain of the wild type XMRV ENV protein consisting of the amino acid sequence SEQ ID NO: 1, (LQNRRGLDILFLKEGGLCAA), said at least one mutation being such that E which is at the position 14 of SEQ ID NO :1 is substituted by R, H or K.

http://www.wipo.int/patentscope/search/en/WO2011092199

There is a very large description:
http://www.wipo.int/patentscope/search/en/detail.jsf?docId=WO2011092199&recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=PCTDescription

From the description:

So, to date, even if XMRV involvement in prostate cancer and CFS appear to be controversial, the eradication of XMRV appears to be a good strategy for the disease treatment.

WO2006/110589 discloses the use of the complete virus for treating prostate cancer. However, this document never demonstrates that wild type virus can be efficiently used for the vaccination of patients.

So, there is a need to provide an efficient drug in order to prevent and/or eradicate XMRV-infection associated diseases, an having an improved efficiency.

One aim of the invention is to provide a new mutated attenuated virus, having enhanced vaccinal efficiency.

Another aim of the invention is to provide a new pharmaceutical composition for treating pathologies.

Retroviruses are viruses, the genome of which is made up of RNA. These viruses are unique in possessing an enzyme that enables synthesis from this RNA of a DNA molecule capable of integrating into the DNA of a host cell. The retrovirus then utilizes the cell machinery to replicate. HIV is one of the best-known retroviruses. Oncogenic retroviruses (or oncoretroviruses) are cancer-causing viruses. Numerous oncoretroviruses are associated with animal diseases.

In humans, two retroviruses, called HTLV and XMRV, have been associated with a type of leukemia and with prostate cancer.

XMRV retrovirus (Xenotropic murine leukemia virus-related virus) belongs to the virus family Retro viridae and the genus gammaretro virus. It has a single-stranded RNA genome that replicates through a DNA intermediate. Its name refers to its close relationship with the murine leukemia viruses ("MuLVs"). The genome, approximately 8100 nucleotides in length, is 95% identical with several endogenous retroviruses of mice, and is 93-94% identical with several exogenous mouse viruses.

 

[Jemal]

This is (part of) the team doing the research I think:

Endogenous Retroviruses and Retroid elements of higher eukaryotes, Thierry Heidmann's founding team

Our laboratory is primarily interested in the study of both infectious and endogenous retroviruses in humans. We have identified a highly conserved domain within the envelope proteins of these elements, which are endowed with immunosuppressive properties and play a critical role in enabling retroviruses to invade their host, allowing cancer cells to escape antitumour immune responses, contributing to the formation of the maternofetal barrier within the placenta of mammals. This research project, encompassing the fields of virology, oncology, immunology and development, gives insights into novel vaccine and therapeutic approaches that take into account the properties of the protein domains newly characterized.

The year 2009 has been highlighted by the identification of the immunosuppressive domain harboured by oncogenic retroviruses of murine (MLV) and human (HTLV, XMRV) origin, and the discovery of specific mutations leading to a marked increase in the immunogenicity of viral antigens, thus allowing us to design novel vaccine approaches. The role of envelope proteins encoded by endogenous retroviruses in placentation has been unambiguously demonstrated through the development of knock-out mice ).

Perspectives

1. Characterization of the mechanisms of immunosuppression mediated by infectious and endogenous retroviruses of human origin at both the cellular and molecular level.
2. Impact of the immunosuppressive function on
- viremia of human pathogenic retroviruses (HTLV, XMRV, HIV),
- cancer progression and tumour immune escape (melanoma, prostate and breast cancer models),
- placentation and maternofetal tolerance (humans, knock-out and knock-in mice, other mammals).
3. Design of therapeutic and vaccine approaches targeting the immunosuppressive domains.

http://www.igr.fr/index.php?p_id=733