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NZ736174B2 - Detection of nucleic acid molecules - Google Patents

Detection of nucleic acid molecules Download PDF

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Publication number
NZ736174B2
NZ736174B2 NZ736174A NZ73617416A NZ736174B2 NZ 736174 B2 NZ736174 B2 NZ 736174B2 NZ 736174 A NZ736174 A NZ 736174A NZ 73617416 A NZ73617416 A NZ 73617416A NZ 736174 B2 NZ736174 B2 NZ 736174B2
Authority
NZ
New Zealand
Prior art keywords
nucleic acid
target nucleic
target
biological sample
batch
Prior art date
Application number
NZ736174A
Other versions
NZ736174A (en
Inventor
Gazanfer Belge
Inga Flor
Meike Spiekermann
Nina Winter
Original Assignee
Mirdetect Gmbh
Filing date
Publication date
Application filed by Mirdetect Gmbh filed Critical Mirdetect Gmbh
Priority claimed from PCT/EP2016/059604 external-priority patent/WO2016174199A1/en
Publication of NZ736174A publication Critical patent/NZ736174A/en
Publication of NZ736174B2 publication Critical patent/NZ736174B2/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/6851Quantitative amplification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/686Polymerase chain reaction [PCR]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2531/00Reactions of nucleic acids characterised by
    • C12Q2531/10Reactions of nucleic acids characterised by the purpose being amplify/increase the copy number of target nucleic acid
    • C12Q2531/113PCR
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2545/00Reactions characterised by their quantitative nature
    • C12Q2545/10Reactions characterised by their quantitative nature the purpose being quantitative analysis
    • C12Q2545/114Reactions characterised by their quantitative nature the purpose being quantitative analysis involving a quantitation step
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/178Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

Abstract

The present invention relates to methods for the detection of target nucleic acids at the lower detection limit, and use of these methods in detecting a disease or disorder in a subject or of determining the extent or progression of a disease or disorder. The target nucleic acid may be DNA or cDNA. In one embodiment, the same target nucleic acid is amplified in parallel preamplification reactions. Equal amounts of the products of the reactions are combined and the level of the target nucleic acid is determined by performing a single quantitative real-time PCR (qRT-PCR).

Claims (15)

1. A method of determining the level of a target nucleic acid in a biological sample, 5 wherein the target nucleic acid is DNA obtained from the biological sample or cDNA obtained from RNA obtained from the biological sample, the method comprising the steps of: (i) providing a batch A sing the target nucleic acid; (ii) providing three or more aliquots of batch A provided in step (i) and performing an independent polymerase chain on (PCR) with each of the three or more aliquots 10 in order to amplify the same single target nucleic acid in each of the three or more aliquots, thereby providing three or more batches B comprising the same amplified target nucleic acid; and (iii) mixing equal amounts of the three or more batches B, thereby providing a batch C, and determining the level of the target nucleic acid in batch C by performing a 15 single quantitative real-time PCR (qRT-PCR), n the level determined in step (iii) corresponds to the expression level of the target nucleic acid in the biological sample.
2. The method of claim 1, wherein the concentration of the target c acid in 20 the biological sample is < 1x10-11 M, or < 1x10-12 M, or < 1x10-13 M, or < 1x10-14 M, or < 1x10-15 M, or < 1x10-16 M.
3. The method of claim 2, wherein the concentration of the target nucleic acid in the biological sample is between 1 M and 7 M, or 2 M and 1x10-17 M, or 25 1x10-13 M and 1x10-17 M, or 1x10-14 and 1x10-17 M, or 1x10-15 and 1x10-17 M, or 1x10-16 and 1x10-17 M.
4. The method of any one of claims 1 to 3, n the target nucleic acid is selected from the group consisting of a target miRNA, a target cell-free circulating DNA, a 30 target mRNA, a target siRNA and a target snRNA.
5. The method of claim 4, wherein the target nucleic acid is a target miRNA.
6. The method of claim 5, n the target miRNA is selected from the group consisting of miR-371a-3p, miR5p, miR-372, miR-373, miR-367 and a-5p.
7. The method of any one of claims 1 to 6, wherein the biological sample is 5 selected from the group consisting of body fluid, tissue, cells, cell lysate and cell culture supernatant.
8. The method of claim 7, wherein the body fluid is selected from the group consisting of blood serum, blood plasma, seminal plasma, hydrocele fluid, spermatocele fluid, 10 whole blood, urine, amniotic fluid, exudate, sputum, saliva and cerebrospinal fluid.
9. The method of claim 7, n the tissue is selected from the group consisting of native tissue, snap-frozen tissue and formalin-fixed and paraffin-embedded (FFPE) tissue. 15
10. The method of claim 7 or 9, wherein the tissue is tumor tissue.
11. The method of any one of claims 1 to 10, wherein batch A comprises cDNA.
12. The method of claim 11, wherein step (i) comprises the steps of: 20 (ia) isolating RNA from the biological sample; and (ib) converting the RNA isolated in step (ia) into cDNA, y providing batch A comprising the cDNA.
13. The method of any one of claims 1 to 12, wherein, in step (ii), three aliquots of 25 batch A are provided.
14. A method of ing a disease or disorder in a subject or of determining the extent or progression of a disease or disorder in a subject, the method comprising the step of: determining the level of a target nucleic acid in biological sample obtained from the 30 subject with the method of any one of claims 1 to 13, n the level of the target nucleic acid in the biological sample is tive of the presence, absence and/or extent or progression of the disease or disorder in the subject.
15. The method of claim 4, wherein the target nucleic acid is a target cell-free circulating DNA, wherein the target cell-free circulating DNA is a target ree circulating tumor DNA. RNA—isciation cDNA-synthesis lification Preampli?caticn Preamplificati‘on‘ l 1 l Real-time PCR Real-time PCR Real-time PCR
NZ736174A 2016-04-29 Detection of nucleic acid molecules NZ736174B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102015106646 2015-04-29
EP15195182 2015-11-18
PCT/EP2016/059604 WO2016174199A1 (en) 2015-04-29 2016-04-29 Detection of nucleic acid molecules

Publications (2)

Publication Number Publication Date
NZ736174A NZ736174A (en) 2024-10-25
NZ736174B2 true NZ736174B2 (en) 2025-01-28

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