Transcription Infidelity, Detection and Uses Thereof
AssigneeTransmedi SA
InventorBernard Bihain
Life of this patent
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Abstract
The present invention relates to the identification of a novel mechanism of transcription infidelity in cells. The invention provides compositions and methods to detect the level of transcript ion infidelity in a sample, as well as the use thereof, e.g., for therapeutic, diagnostic, pharmacogenomic or drug design. As will be disclosed, the invention is particularly suited for detecting, monitoring or treating proliferative cell disorders, for the design and/or screening of drugs, for patient or disease profiling, prediction of disease severity and evaluation of drug efficacy.
Claims17
1-27. (canceled)
A method of detecting the presence or stage of a disease in a subject, the method comprising assessing in vitro or ex vivo the presence or rate of transcription infidelity in a sample from said subject, said presence or rate being an indication of the presence or stage of a disease in said subject.
A method of screening, identifying or optimising a drug, the method comprising a step of assessing whether said drug alters the rate of transcription infidelity of a gene.
A method of modifying a mammalian gene to make it resistant or sensitive to transcription infidelity for use in a method of treatment of a human or animal, particularly for treating a proliferative cell disorder.
A method of assessing the efficacy of a drug or candidate drug, the method comprising a step of assessing whether said drug alters the rate of transcription infidelity of a mammalian gene, such an alteration being an indication of drug efficacy.
A method of identifying or producing biomarkers, the method comprising identifying, in a sample from a subject, the presence of transcription infidelity site(s) in a target protein, RNA or gene and, optionally, determining the sequence of said transcription infidelity site(s).
A method of identifying or producing ligands specific for a trait or pathological condition, the method comprising identifying, in a sample from a subject having said trait or pathological condition, the presence of at least one transcription infidelity site in one or several target proteins or genes, optionally determining the sequence of said at least one transcription infidelity site, and producing a ligand that specifically binds to said at least one transcription infidelity site.
A composition of matter comprising:
- a) a synthetic peptide comprising a domain of a TI-protein;
- b) a synthetic peptide comprising a domain of a TI-protein, wherein said transcription infidelity site comprises at least one modification encoded by a nucleic acid alteration obeying to the following rules:
- Substitution of A occurs when A is preceded or followed by C,
- Substitution of T occurs when T is preceded or followed by G,
- Substitution of C occurs when C is preceded by G or A, and
- Substitution of G occurs when G is preceded or followed by A;
- c) a synthetic peptide comprising a domain of a TI-protein, wherein said peptide comprises the sequence of a C-terminal fragment of said protein comprising at least one amino acid variation caused by transcription infidelity, and/or comprises less than 100 amino acids;
- d) a synthetic peptide comprising a domain of a TI-protein, wherein said transcription infidelity site comprises at least one modification encoded by a nucleic acid alteration obeying to the following rules:
- Substitution of A occurs when A is preceded or followed by C,
- Substitution of T occurs when T is preceded or followed by G,
- Substitution of C occurs when C is preceded by G or A, and
- Substitution of G occurs when G is preceded or followed by A;
- and
- said peptide comprises the sequence of a C-terminal fragment of said protein comprising at least one amino acid variation caused by transcription infidelity, and/or comprises less than 100 amino acids;
- e) a peptide comprising a sequence selected from SEQ ID NOs:
- 1 to 32;
- f) a synthetic nucleic acid molecule comprising the sequence of a transcription infidelity site of an RNA molecule;
- g) an antibody, a nucleic acid primer or a nucleic acid probe that specifically binds a transcription infidelity site of a protein or RNA;
- h) an antibody that specifically binds a domain of a TI-protein, or a derivative of such an antibody having substantially the same antigen specificity;
- or
- i) an antibody or derivative thereof that specifically binds to a domain of a TI-protein, wherein said antibody is conjugated to a molecule, a drug, a label, a toxic molecule or a radioisotope.
Dependencies are inferred from the claim text.