WO2002033120B1 - Non-invasive prenatal monitoring - Google Patents

Non-invasive prenatal monitoring

Info

Publication number
WO2002033120B1
WO2002033120B1 PCT/GB2001/004629 GB0104629W WO0233120B1 WO 2002033120 B1 WO2002033120 B1 WO 2002033120B1 GB 0104629 W GB0104629 W GB 0104629W WO 0233120 B1 WO0233120 B1 WO 0233120B1
Authority
WO
WIPO (PCT)
Prior art keywords
rna
fetal
maternal
sample
detecting
Prior art date
Application number
PCT/GB2001/004629
Other languages
French (fr)
Other versions
WO2002033120A2 (en
WO2002033120A3 (en
Inventor
Yuk Ming Dennis Lo
Lit Man Poon
Original Assignee
Univ Hong Kong Chinese
Yuk Ming Dennis Lo
Lit Man Poon
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Hong Kong Chinese, Yuk Ming Dennis Lo, Lit Man Poon filed Critical Univ Hong Kong Chinese
Priority to AU2001295738A priority Critical patent/AU2001295738A1/en
Publication of WO2002033120A2 publication Critical patent/WO2002033120A2/en
Publication of WO2002033120A3 publication Critical patent/WO2002033120A3/en
Publication of WO2002033120B1 publication Critical patent/WO2002033120B1/en
Priority to HK04101313A priority patent/HK1058529A1/en

Links

Classifications

    • 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
    • C12Q1/6879Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
    • 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
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

Abstract

Embodiments of the present invention are directed to the detection of fetal or maternal RNA in a blood sample from a pregnant subject, and may involve subjecting the sample to a test for fetal or maternal analysis indicative of a fetal or maternal condition or characteristics. For instance, the RNA analysis may involve the assessment of the gene expression pattern of an unborn fetus by analysing a blood sample from the mother. The prenatal monitoring technology allows, for the first time, the detection of genes which are expressed by the fetus, just by analysis of a sample of maternal blood. In specific embodiments, the prenatal monitoring technology is based on the discovery of circulating RNA of fetal origin in the plasma of pregnant women. In general, the detection method performed on a maternal serum or plasma sample from a pregnant female comprises detecting the presence of RNA of fetal or maternal original in the sample.

Claims

AMENDED CLAIMS[received by the International Bureau on 14 October 2002 (14.10.02); original claims 1-27 replaced by amended claims 1-26 (4 pages)]
1. A method of performing prenatal monitoring or testing of a blood sample obtained from a pregnant subject, the method comprising: removing all or substantially all nucleated and anucleated cell populations from the blood sample to obtain a remaining material; amplifying a nucleic acid from the remaining material and subjecting the nucleic acid to a test for fetal or maternal RNA analysis indicative of a fetal or maternal condition or characteristic resulting from the pregnancy of the pregnant subject.
2. The method according to claim 1 wherein all nucleated and anucleated cell populations are removed from the blood sample to obtain the remaining material.
3. The method according to claim 1 wherein the remaining material comprises non-cellular matter, and wherein the RNA analysis is performed on the non- cellular matter of the remaining material.
4. The method according to claim 1 wherein the remaining material comprises cellular matter, and wherein the RNA analysis is performed on the cellular matter of the remaining material.
5. The method according to claim 1 wherein the remaining material comprises plasma.
6. The method according to claim 1 wherein the remaining material comprises serum.
7. A detection method performed on a maternal serum or plasma sample from a pregnant female, the method comprising: amplifying a nucleic acid from the maternal serum or plasma sample; and detecting the presence of RNA of fetal origin in the sample.
8. The method according to claim 7 further comprising amplifying the fetal RNA to facilitate detecting the presence of RNA of fetal origin in the sample.
9. The method according to claim 8 wherein the fetal RNA is converted into complementary DNA by a reverse transcriptase and then detected by a polymerase chain reaction.
10. The method according to claim 8 or claim 9 wherein at least one fetal sequence specific oligonucleotide is used in amplifying the fetal RNA.
11. The method according to claim any one of claims 7 to 10 wherein the fetal RNA is detected using a sequence specific probe.
12. The method according to claim any one of claims 7 to 11 wherein detecting the presence of RNA of fetal origin in the sample comprises detecting the presence of a fetal RNA transcribed from the Y chromosome.
13. The method according to claim 12 wherein the fetal RNA is transcribed from the ZFY gene.
14. The method according to claim 12 or claim 13 further comprising determining the sex of the fetus from the RNA of fetal origin in the sample.
15. The method according to claim any one of claims 7 to 11 wherein detecting the presence of RNA of fetal origin in the sample comprises detecting the presence of a fetal RNA transcribed from a gene or other DNA sequences inherited from the father or the mother.
16. The method according to claim any one of claims 7 to 11 wherein the RNA is detected by any one of a physical method, an immunological method, and a biochemical method.
17. A detection method performed on a maternal serum or plasma sample from a pregnant female, the method comprising: amplifying a nucleic acid from the maternal serum or plasma sample; and detecting the presence of RNA of fetal or maternal origin in the sample.
18. The method according to claim 17 further comprising amplifying the fetal or maternal RNA to facilitate detecting the presence of RNA of fetal or maternal origin in the sample.
13
19. The method according to claim 18 wherein the fetal or maternal RNA is converted into complementary DNA by reverse transcriptase and then detected by a polymerase chain reaction.
20. The method according to claim 18 or claim 19 wherein at least one fetal or maternal sequence specific oligonucleotide is used in amplifying the fetal or maternal RNA resulting from the pregnancy of the pregnant female.
21. The method according to claim any one of claims 17 to 20 wherein the fetal or maternal RNA is detected using a sequence specific probe.
22. The method according to claim any one of claims 17 to 21 wherein detecting the presence of RNA of fetal or maternal origin in the sample comprises detecting the presence of RNA transcribed from genes on chromosome 6.
23. The method according to claim 22 wherein the RNA is transcribed from the HLA-G gene.
24. A method of performing prenatal monitoring or testing, the method comprising the steps of:
(i) providing a maternal blood sample;
(ii) separating the sample into a predominantly cellular fraction (fraction 1) and a predominantly non-cellular fraction (fraction 2);
(iii) detecting the presence of RNA of fetal origin in fraction 2;
(iv) providing a diagnosis based on at least one of the presence, quantity, concentration, sequence, and biochemical composition of the detected RNA.
25. The method according to claim 24 further comprising the step of allowing clotting in the maternal blood sample to obtain a serum and using the serum for steps (iii) and (iv).
14
26. A method of performing a prenatal monitoring or testing on a maternal blood sample of a pregnant subject, the method comprising: obtaining a non-cellular fraction of the maternal blood sample; amplifying a nucleic acid from the non-cellular fraction; and performing an RNA analysis on the nucleic acid for expressed human genes of fetal or maternal origin resulting from the pregnancy of the pregnant subject.
15
PCT/GB2001/004629 2000-10-17 2001-10-17 Non-invasive prenatal monitoring WO2002033120A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2001295738A AU2001295738A1 (en) 2000-10-17 2001-10-17 Non-invasive prenatal monitoring
HK04101313A HK1058529A1 (en) 2000-10-17 2004-02-24 Non-invasive prenatal monitoring.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US24141700P 2000-10-17 2000-10-17
US60/241,417 2000-10-17
US09/876,005 2001-06-06
US09/876,005 US6664056B2 (en) 2000-10-17 2001-06-06 Non-invasive prenatal monitoring

Publications (3)

Publication Number Publication Date
WO2002033120A2 WO2002033120A2 (en) 2002-04-25
WO2002033120A3 WO2002033120A3 (en) 2002-12-27
WO2002033120B1 true WO2002033120B1 (en) 2003-02-20

Family

ID=26934284

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/004629 WO2002033120A2 (en) 2000-10-17 2001-10-17 Non-invasive prenatal monitoring

Country Status (5)

Country Link
US (1) US6664056B2 (en)
CN (1) CN1219074C (en)
AU (1) AU2001295738A1 (en)
HK (1) HK1058529A1 (en)
WO (1) WO2002033120A2 (en)

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AU2001295738A1 (en) 2002-04-29
CN1469932A (en) 2004-01-21
CN1219074C (en) 2005-09-14
US6664056B2 (en) 2003-12-16
WO2002033120A2 (en) 2002-04-25
HK1058529A1 (en) 2004-05-21
US20020045176A1 (en) 2002-04-18
WO2002033120A3 (en) 2002-12-27

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