Specific TT virus sequences and chimeric TT virus host cell DNA molecules for use in diagnosis, prevention and treatment of cancer and autoimmunity

Abstract

Described are single-stranded new sequences of TT viruses, rearranged TTV sequences and hybrid molecules of a specific TT virus sequence and host cell DNA that are capable of replicating autonomously for use in diagnosis, prevention and treatment of diseases like cancer and autoimmunity. In addition, it relates to the use of such molecules as gene vectors and artificial chromosomes.

Description

FIELD OF THE INVENTION[0001]The present invention relates to single-stranded new sequences of TT viruses and hybrid molecules of a specific TT virus sequence and host cell DNA that are capable of replicating autonomously for use in diagnosis, prevention and treatment of diseases like cancer and autoimmunity. In addition, it relates to the use of such molecules as gene vectors and artificial chromosomes.BACKGROUND OF THE TECHNOLOGY[0002]Since their discovery in 1997 by Okamoto and colleagues TT viruses (TTV) have been found to be widely spread in all human populations, in domestic animals, and in old world primates (1,2). A large number of types and pseudotypes have been identified in humans, pointing to a remarkable heterogeneity of this virus family now being assigned as a new virus family, Anelloviridae (3). Viral DNA can be demonstrated in sera of almost every human being and some reports even document such DNA in newborn children and cord blood, suggesting prenatal transmission ...

AI Technical Summary

Benefits of technology

[0008]The previous considerations are summarized in FIG. 4. Obviously, the recombination between the TTV regulatory region and cellular nucleic acids must be a relatively frequent process, since such recombinants are found in the majority of cell lines thus far analyzed. It also should contribute to cell proliferation, otherwise the regular persistence of such molecules, in part over decades of continuous proliferation, would be difficult to explain. It is assumed that this type of recombination is a random process, involving different types of cellular genes. The coding function of the TTV HCR and / or the uptake of genes steering cell proliferation, or blocking the function of proliferation antagonists, or inhibiting cell differentiation should lead to an accumulation of cells containing these types of recombinants. It is envisaged that this, in combination with additional mutational or recombinational events of the cells harbouring such TTV-host cell nucleic acid recombinants, provides a selective advantage for cells carrying such episomes. The presence of the latter would represent a prime risk factor for malignant conversion. In this sense those recombinations should be of general importance for different types of human cancers, although a certain degree of specificity for a limited set of genes would be expected for individual cancer types.

[0009]The implications of this model are profound. They reach from cancer prevention, early detection into cancer therapy. The important role of TTV infections and of the persistence of TTV HCR is stressed by the available information. Prevention of these infections should reduce the risk for the development of the described recombinants. The diagnosis of specific recombinants would probably contribute to cancer risk assessment. Profound implications would be expected for cancer therapy: the TTV HCR emerges as the prime determinant for the persistence and maintenance of the single-stranded episomes. Since this region appears to be part of an open reading frame, it should be vulnerable to small interfering RNAs or DNAs. Thus, it offers a suitable target for future therapeutic deliberations.

Problems solved by technology

In spite of the widespread occurrence of these viruses, intensive research performed during more than 10 years failed to demonstrate a pathogenic role of such infections in human disease.

In addition, TT viruses frequently reveal intramolecular rearrangements which lead to subviral DNA genomes in part defective and with novel open reading frames.

Yet, the ubiquity of these infections rendered an interpretation of these results rather difficult and did not permit a linkage of these observations with tumor development.

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