Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1995-03-27
1998-05-05
Jones, W. Gary
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 71, 435 723, 435 79, 435 912, 435174, 4352872, 536 231, 536 243, 536 2433, 5303881, C12Q 168, C12P 1934, C07H 2102, C07H 2104
Patent
active
057472505
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention concerns a new therapeutic or diagnostic agent which contains at least one nucleic acid as the active substance and is particularly suitable for the diagnosis or/and therapy of tumours. Diagnostic and therapeutic methods using these materials are also features of the invention.
BACKGROUND AND PRIOR ART
Proteins which contain a homeobox play an important role in the development of multicellular differentiated tissue. It is assumed that transcriptional regulation by the homeobox proteins coordinates the exact spatial and chronological sequence of growth and differentiation in the developing embryo. It is known from the literature (see e.g. K. Kongsuwan, J. M. Adams, Nucleic Acids Res. 17 (1989), 1881-1891; C. Blatt, D. Aberdam, R. Schwartz, L. Sachs, EMBO J. 7 (1988), 4283-4290; C. Blatt, Cancer Cells 2 (1990), 186-189; T. H. Rabbitts Cell 647 (1991), 641-644; A. W. Sasaki, J. Doskow, C. L. Macleod, M. B. Rodgers, L. J. Goudas, M. F. Wilkinson, MOD34 (1991), 155-164)) that some genes containing a homeobox are connected with oncogenesis.
A multigene family which has a common conserved sequence motif, the "paired"-box, is also connected with developmental control and tissue specificity in various organisms. The "paired" domain coded by the "paired" box represents a DNA-binding domain (J. Treisman, E. Harris, C. Desplan, Genes. Dev. 5 (1991), 594-604; G. Chalepakis, R. Fritsch, H. Fickenscher, 0. Deutsch, M. Goulding, P. Gruss, Cell 66 (1991), 873-884) and has been identified in various organisms such as Drosophila, mouse, tortoise, zebra fish, nematodes and humans. There has not yet been known to be a connection between the "paired" domain and oncogenesis. Great efforts are made in medical research to provide new therapeutic and diagnostic agents related to the development of tumours. The object of the present invention is to provide a new agent which is particularly suitable for the diagnosis and therapy of tumours.
SUMMARY OF THE INVENTION
The object according to the invention is achieved by a process for the production of an agent for tumour diagnostics or/and tumour therapy and methods of using the agent, wherein the agent is characterized in that it comprises
If desired together with common pharmaceutical carrier substances, auxiliary substances and diluents.
Surprisingly it was found that Pax proteins, i.e. proteins which contain the "paired" domain, can promote oncogenesis and can therefore be classified as a new group of strong oncoproteins which induce cell proliferation, anchor-independent growth and angiogenesis. It was found that cells transformed with Pax genes exhibit all the classical signs of malignancy such as e.g. contact inhibition in the focus assay, growth in soft agar and tumour induction in the nude mouse.
The therapeutic or diagnostic agent according to the invention can therefore be used as a molecular probe in tumour diagnostics since the use of a nucleic acid which hybridizes with a nucleotide sequence coding for a Pax protein enables a qualitative and quantitative, cell- and tissue-specific determination of the expression of the respective Pax gene.
However, the agent according to the invention is also suitable as an antisense nucleic acid for the specific inhibition of the expression of genes which contain the Pax sequence and is thus also suitable as a therapeutic agent.
For a diagnostic test or/and for a therapeutic treatment an agent according to the invention must contain at least one nucleic acid molecule which hybridizes to a Pax gene. The nucleic acid according to the invention preferably hybridizes under "stringent conditions" to a Pax gene. Stringent conditions within the meaning of the present invention are defined as those conditions that enable a selective and detectable specific binding of the nucleic acid to a particular Pax gene or to several Pax genes or Pax transcripts. Such a hybridization under stringent conditions preferably means that binding of the probe to the Pax gene or to the Pax RNA is still detectable a
REFERENCES:
Frazier et al. J. Cell Physiol 133: 169-174 (abstract), 1987.
Ishiwata et al. Exp. Pathology 41: 1-9 (abstract), 1991.
Dressler et al PNAS 89 1179-1183, 1992.
Gruss Peter
Maulbecker Catharina
Jones W. Gary
Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.v.
Rees Dianne
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