CN106053848A - Kit for oculopathy detection and detection method - Google Patents
Kit for oculopathy detection and detection method Download PDFInfo
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- CN106053848A CN106053848A CN201610629367.9A CN201610629367A CN106053848A CN 106053848 A CN106053848 A CN 106053848A CN 201610629367 A CN201610629367 A CN 201610629367A CN 106053848 A CN106053848 A CN 106053848A
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- sicam
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/16—Aptamers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/70525—ICAM molecules, e.g. CD50, CD54, CD102
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/046—Thyroid disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/16—Ophthalmology
Abstract
The invention discloses an aptamer specially bonded with sICAM-1 and a kit. The provided aptamer has preferable affinity for sICAM-1 and can capture sICAM-1 in a solution. A kit prepared from the aptamer is used for screening oculopathy. The kit has characteristics of high sensitivity and low cost and is suitable for large-scale screening.
Description
Technical field
The present invention relates to a kind of test kit for detecting oculopathy and detection method thereof.
Background technology
Thyroid-associated ophthalmopathy (thyroid associated ophthalmopathy, TAO) is the common disease of department of endocrinology
One of sick, also it is to treat one of disease the most difficult at present in the world.The TAO course of disease is longer, and each age group all can occur, with female
Property is multiple.The lighter can affect life, work quality, damages appearance, and severe one may result in visual deterioration, the most blind, carries to patient
Heavy economy and psychological burden are come.In recent years, due to living-pattern preservation, the increase of operating pressure, social environment shape
The factors such as the change of condition, popularizing of edible iodized salt, and irregular medication, the sickness rate of TAO substantially rises, and admission rate is high.
The brightest due to primary disease reason at present, clinical main with hormone, immunosuppressant, growth hormone analogs, antithyroid drug, socket of the eye
The Comprehensive Treatments such as interior radiation, orbital decompression are main, but for various reasons, effect is the most unsatisfactory, there is no up to now and appoint
TAO can effectively be treated by what a kind of medicine, and obtains long-term remission.Therefore, the medicine of research treatment thyroid-associated ophthalmopathy is urgently
Solve the technical problem that.And detect the direction that described disease this area especially is actively studied.
Recent studies indicate that, the expression of intercellular adhesion molecule-1 and Autoimmune thyroid disease immunopathology
Closely related.SICAM-1 and the sICAM-1 table of lymphocyte infiltration, endotheliocyte in the parathyroid tissue of thyroiditis patient
Reach Showed Very Brisk.Additionally, it was found that increase with patients serum's sICAM-1 horizontal abnormality of expophthalmos, this is because after patient's eyeball
Tissue strong expression sICAM-1, so the level that serum sICAM-1 raises is how closely related with socket of the eye week inflammatory infiltration degree.This
Outward, research also finds, in the therapeutic process of medicine, and thyroid function and the improvement of clinical symptoms and Serum sICAM-1
Decline asynchronous, often the recovery of thyroid function to a great extent will be early than the recovery of sICAM-1.In sum,
The concentration change of Soluble ICAM-1 is possibly for judging that the autoimmune disorder level of GD, drug withdrawal whether and are
No recurrences etc. are significant.The expression of intercellular adhesion molecule-1 and thyroid-associated ophthalmopathy have direct correlation, therefore, and inspection
Survey the expression of intercellular adhesion molecule-1, be used directly for identifying thyroid-associated ophthalmopathy.But traditional detection is thin
The expression of ICAM-1 has operation complexity, time-consuming shortcoming.
Aptamer (Aptamer, also known as aptamers, aptamer) is can high-affinity, certain life of combination of high specific
Thing leather El target strand widow's nucleic acid molecules (ssDNA or ssRNA).Aptamer is by index concentration Fas lignand system evolution technology
(Systemat1c Evolut1on of L1gands by Exponent1al enr1chment, SELEX) is from synthetic
What in DNA/RNA library, screening obtained can combine the single stranded DNA/RNA of target molecules by high degree of specificity.Report aptamer
Target include metal ion, organic molecule, polypeptide, protein, cell even tissue etc..The molecular recognition merit of aptamer
Can be similar with antibody, there is the target identification ability the most higher with antibody molecule, but have the most excellent compared with antibody
Good characteristic, as molecular weight is little, can manufacture, not easy in inactivation, non-immunogenicity, be readily synthesized with labelling, quickly penetrate
Between tissue, good dynamic metabolism, different batches, product does not haves difference and has fine chemical stability, at biology
The fields such as detection, medical diagnosis on disease treatment have important application prospect.
Summary of the invention
It is an object of the invention to provide aptamer and the test kit thereof of a kind of specific bond sICAM-1.
The aptamer that the present invention provides, is the single stranded DNA shown in sequence 1-15 of sequence table.
Described aptamer and sICAM-1 albumen have preferable affinity.
Also described aptamer can be modified or transformed, obtain the derivant of described aptamer.
The derivant of described aptamer can be following any one:
A) described aptamer being deleted part or increases the nucleotide of partial complementarity, obtain has with described aptamer
There is the derivant of the aptamer of identical function;
B) described aptamer carrying out nucleotide replacement or part is modified, obtain has identical with described aptamer
The derivant of the aptamer of function;
C) transforming the skeleton of described aptamer as phosphorothioate backbone, obtain has phase with described aptamer
The derivant of the aptamer of congenerous;
D) aptamer transform peptide nucleic acid(PNA) as, obtain has the aptamer of identical function with described aptamer
Derivant;
E) after described aptamer being connected upper fluorescence, radioactivity and therapeutic substance, that obtain with described aptamer
There is the derivant of the aptamer of identical function.
Described aptamer can be used for the test kit of preparation detection sICAM-1.
Utilize the aptamer of the present invention, the sICAM-1 in blood can be captured, thus sieve for thyroid-associated ophthalmopathy
Look into.Utilize the aptamer of the present invention, part to replace monoclonal antibody capture sICAM-1 to detect, there is highly sensitive, cost
Preparation low, easy, the advantage easily preserved.The present invention has the highest using value.
Detailed description of the invention
Below example facilitates a better understanding of the present invention, but does not limit the present invention.Experiment in following embodiment
Method, if no special instructions, is conventional method.
Embodiment 1, the screening of aptamer and preparation
Two ends comprise about 20 nucleotide, centre includes that the random nucleic acid library of 39 nucleotide is as follows in design:
5’-ACGACTAACGTGTAACAG(N39)CAGTGCATGATGCTACGAA-3’;N39 represents 39 random nucleoside
Acid.
Being double-stranded DNA by single-stranded DNA banks amplification, product is through 2% agarose gel electrophoresis and cuts glue recovery purification;To return
The double-stranded DNA received is template, and in vitro transcription goes out single stranded RNA random library, and transcription product is through PAGE purification.75 μ g RNA library warps
The anti-sieve of nitrocellulose filter removes the RNA molecule being combined with film, and then (by Chen Zhihong etc., people is thin with 2ug sICAM-1 albumen
The eukaryotic cell expression of intercellular adhesion molecule-1 and the method disclosed in qualification, express the destination protein obtained), hatch for 37 DEG C
30min, reactant liquor filters through nitrocellulose filter, washs filter membrane;Then filter membrane is shredded, be placed in elution buffer (6mol/L
Carbamide, 0.55mol/L ammonium acetate, l.5mmol/L EDTA, 0.15%SDS) in boil 5min, centrifugal, take supernatant, dehydrated alcohol
Precipitation RNA, and be redissolved in 20 μ 1DEPC water;With RNA for template RT-PCR amplifying doulbe-chain DNA, in vitro transcription goes out RNA literary composition
Storehouse is screened for next round;Often wheel screening process in RT-PCR obtain double-stranded DNA library, with this double-stranded DNA as template body outside turn
Recording out RNA aptamer storehouse, screening carries out 10 altogether and takes turns.Having obtained 15 aptamers, its sequence is respectively SEQ ID NO:1-15 institute
Show.Particular sequence is as follows:
SICAM-1-1:
ACGACTAACGTGTAACAGTCCAAGTATTCATACATACCATAAATTCATTGTCATTAACAGTGCATGATGCTACGAA
(SEQ ID NO:1)
SICAM-1-2:
ACGACTAACGTGTAACAGCAGACACCATATATACTATCTACTACCACATACCTCTACCAGTGCATGATGCTACGAA
(SEQ ID NO:2)
SICAM-1-3:
ACGACTAACGTGTAACAGCTAACTTCTTATAACTTAAGATACTTCTTCCAAACAACACAGTGCATGATGCTACGAA
(SEQ ID NO:3)
SICAM-1-4:
ACGACTAACGTGTAACAGTACATCACTCTAATCTTCACGCCTCAGTTACATTCCCTTCAGTGCATGATGCTACGAA
(SEQ ID NO:4)
SICAM-1-5:
ACGACTAACGTGTAACAGATGTATATTCCTTATATGACTATAATTCTTACCTATAAACAGTGCATGATGCTACGAA
(SEQ ID NO:5)
SICAM-1-6:
ACGACTAACGTGTAACAGACCTCTATCTCACTCTTCCCTTTCGCCTACACATCCGAACAGTGCATGATGCTACGAA
(SEQ ID NO:6)
SICAM-1-7:
ACGACTAACGTGTAACAGAGATTCACTAATATTTCTTCGCCTCGCCATACTTAAGATCAGTGCATGATGCTACGAA
(SEQ ID NO:7)
SICAM-1-8:
ACGACTAACGTGTAACAGTACCCATCCACCTTCTTACTACTGCTCTCTCAATCTACACAGTGCATGATGCTACGAA
(SEQ ID NO:8)
SICAM-1-9:
ACGACTAACGTGTAACAGACAGATACATTCATATCAAGTTACACATCTCCATGTTAACAGTGCATGATGCTACGAA
(SEQ ID NO:9)
SICAM-1-10:
ACGACTAACGTGTAACAGCAGAACACAAATCTATACAAATCAGCATCACACTCATACCAGTGCATGATGCTACGAA
(SEQ ID NO:10)
SICAM-1-11:
ACGACTAACGTGTAACAGATACCAATCGCCACCTACACTTACATCTAGACACTCTATCAGTGCATGATGCTACGAA
(SEQ ID NO:11)
SICAM-1-12:
ACGACTAACGTGTAACAGTATCTACACATAGATCCTCCACTTAATAACAATCTGTCACAGTGCATGATGCTACGAA
(SEQ ID NO:12)
SICAM-1-13:
ACGACTAACGTGTAACAGATACCTCATCAGATATTACATTCGCCAATATTTCTCTATCAGTGCATGATGCTACGAA
(SEQ ID NO:13)
SICAM-1-14:
ACGACTAACGTGTAACAGTCTATAACGCCTAACTACACCACTCCACTCATTATAATACAGTGCATGATGCTACGAA
(SEQ ID NO:14)
SICAM-1-15:
ACGACTAACGTGTAACAGATCTATTTCACCATTAAGAACCATATCGCATCACCCTTCCAGTGCATGATGCTACGAA
(SEQ ID NO:15)
The performance measurement of embodiment 2 sICAM-1 protein binding aptamer
RNA aptamer taking 2.0 μ g respectively, digests lh with calf intestinal alkaline phosphatase (CIP) 37 DEG C, purification reclaims dephosphorization
The RNA of acidifying;By T4 polynucleotide kinase labelling [γ-32P] ATP in dephosphorylized RNA molecule end.10nmol radiates
Property labelling RNA aptamer sICAM-1 37 DEG C with variable concentrations (1-200nM) respectively hatch 30min, each group reactant liquor warp
Nitrocellulose filter filters, and washs filter membrane, is dried filter membrane, and liquid scintillation counter measures the exit dose of residual, same sample on filter membrane
Parallel do twice mensuration.Calculate the dissociation constant of each aptamer and sICAM-1.Result is as follows:
Title | Dissociation constant Kd (unit nM) |
sICAM-1-1 | 8.8 |
sICAM-1-2 | 8.9 |
sICAM-1-3 | 9.0 |
sICAM-1-4 | 7.9 |
sICAM-1-5 | 8.3 |
sICAM-1-6 | 8.2 |
sICAM-1-7 | 8.9 |
sICAM-1-8 | 9.3 |
sICAM-1-9 | 8.7 |
sICAM-1-10 | 8.1 |
sICAM-1-11 | 8.0 |
sICAM-1-12 | 9.4 |
sICAM-1-13 | 7.8 |
sICAM-1-14 | 8.6 |
sICAM-1-15 | 8.9 |
PBS blank | Without binding ability |
Aptamer specificity analyses and stability analysis described in embodiment 3
It is respectively adopted human albumin, immune globulin, vibrio cholera VgrG3C albumen, escherichia coli outer membrane protein
A, Lp-PLA2 albumen, carries out specific detection with 15 aptamers, through binding tests find, these aptamers the most not with this
A little albumen combine, and are only combined the specificity keeping higher with sICAM-1.
By described aptamer, take 0.2ug, be respectively placed in the serum of room temperature, aqueous solution, place two weeks.Pass through RT-
PCR detects, and finds its Stability Analysis of Structures of placement of two weeks, is not degraded.
The diagnosis of aptamer disease described in embodiment 4
By 15 aptamers respectively with the blood mixing 30min of 10 Patients with Thyroid Associated Ophthalmopathies and normal person, logical
Cross biotin to separate, the content of quantitative analysis sICAM-1 therein albumen, found by analysis, 10 thyroid-associated ophthalmopathies
In patient, the content of sICAM-1 albumen dramatically increases relative to normal person.
These are only the preferred embodiments of the present invention, be not limited to the present invention, for those skilled in the art
For Yuan, all any modification, equivalent substitution and improvement etc. done within the spirit and principles in the present invention, should be included in this
Within the protection domain of invention.
Sequence table
< 110 > Li Qian
< 120 > mono-kind is for detecting test kit and the detection method thereof of oculopathy
〈160〉14
〈210〉1
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-1:
ACGACTAACGTGTAACAGTCCAAGTATTCATACATACCATAAATTCATTGTCATTAA
CAGTGCATGATGCTACGAA
〈210〉2
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-2:
ACGACTAACGTGTAACAGCAGACACCATATATACTATCTACTACCACATACCTCTAC
CAGTGCATGATGCTACGAA
〈210〉3
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-3:
ACGACTAACGTGTAACAGCTAACTTCTTATAACTTAAGATACTTCTTCCAAACAACA
CAGTGCATGATGCTACGAA
〈210〉4
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-4:
ACGACTAACGTGTAACAGTACATCACTCTAATCTTCACGCCTCAGTTACATTCCCTT
CAGTGCATGATGCTACGAA
〈210〉5
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-5:
ACGACTAACGTGTAACAGATGTATATTCCTTATATGACTATAATTCTTACCTATAAA
CAGTGCATGATGCTACGAA
〈210〉6
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-6:
ACGACTAACGTGTAACAGACCTCTATCTCACTCTTCCCTTTCGCCTACACATCCGAA
CAGTGCATGATGCTACGAA
〈210〉7
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-7:
ACGACTAACGTGTAACAGAGATTCACTAATATTTCTTCGCCTCGCCATACTTAAGAT
CAGTGCATGATGCTACGAA
〈210〉8
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-8:
ACGACTAACGTGTAACAGTACCCATCCACCTTCTTACTACTGCTCTCTCAATCTACA
CAGTGCATGATGCTACGAA
〈210〉9
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-9:
ACGACTAACGTGTAACAGACAGATACATTCATATCAAGTTACACATCTCCATGTTAA
CAGTGCATGATGCTACGAA
〈210〉10
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-10:
ACGACTAACGTGTAACAGCAGAACACAAATCTATACAAATCAGCATCACACTCATAC
CAGTGCATGATGCTACGAA
〈210〉11
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-11:
ACGACTAACGTGTAACAGATACCAATCGCCACCTACACTTACATCTAGACACTCTAT
CAGTGCATGATGCTACGAA
〈210〉12
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-12:
ACGACTAACGTGTAACAGTATCTACACATAGATCCTCCACTTAATAACAATCTGTCA
CAGTGCATGATGCTACGAA
〈210〉13
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-13:
ACGACTAACGTGTAACAGATACCTCATCAGATATTACATTCGCCAATATTTCTCTAT
CAGTGCATGATGCTACGAA
〈210〉14
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-14:
ACGACTAACGTGTAACAGTCTATAACGCCTAACTACACCACTCCACTCATTATAATA
CAGTGCATGATGCTACGAA
〈210〉15
〈211〉76
〈212〉DNA
< 213 > artificial sequence
< 400 > sICAM-1-15:
ACGACTAACGTGTAACAGATCTATTTCACCATTAAGAACCATATCGCATCACCCTTC
CAGTGCATGATGCTACGAA
Claims (5)
1. the test kit for oculopathy detection, it is characterised in that: comprise aptamer.
2. test kit as claimed in claim 1, it is characterised in that: described aptamer is described in SEQ ID No:7.
3. the fit application in the test kit of preparation detection oculopathy described in SEQ ID No:7.
4. the test kit as described in claim 1-2, it is characterised in that: described oculopathy is thyroid-associated ophthalmopathy.
Apply the most as claimed in claim 3, it is characterised in that: described oculopathy is thyroid-associated ophthalmopathy.
Priority Applications (1)
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CN201610629367.9A CN106053848A (en) | 2015-11-01 | 2015-11-01 | Kit for oculopathy detection and detection method |
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Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610629367.9A CN106053848A (en) | 2015-11-01 | 2015-11-01 | Kit for oculopathy detection and detection method |
CN201510723711.6A CN105334327B (en) | 2015-11-01 | 2015-11-01 | Kit and method for detecting ophthalmopathy |
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CN201510723711.6A Division CN105334327B (en) | 2015-11-01 | 2015-11-01 | Kit and method for detecting ophthalmopathy |
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CN201610629097.1A Withdrawn CN105974140A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628671.1A Withdrawn CN106018834A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method thereof |
CN201610628761.0A Withdrawn CN106199008A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628596.9A Withdrawn CN105974138A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628554.5A Withdrawn CN106248964A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628672.6A Withdrawn CN105974139A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628675.XA Withdrawn CN106018835A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method thereof |
CN201610628827.6A Withdrawn CN106248965A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610629366.4A Withdrawn CN106199009A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610629215.9A Withdrawn CN106248966A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201510723711.6A Active CN105334327B (en) | 2015-11-01 | 2015-11-01 | Kit and method for detecting ophthalmopathy |
CN201610628509.XA Withdrawn CN106199006A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628510.2A Withdrawn CN105974137A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610629367.9A Withdrawn CN106053848A (en) | 2015-11-01 | 2015-11-01 | Kit for oculopathy detection and detection method |
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CN201610629097.1A Withdrawn CN105974140A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628671.1A Withdrawn CN106018834A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method thereof |
CN201610628761.0A Withdrawn CN106199008A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628596.9A Withdrawn CN105974138A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628554.5A Withdrawn CN106248964A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628672.6A Withdrawn CN105974139A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
CN201610628675.XA Withdrawn CN106018835A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method thereof |
CN201610628827.6A Withdrawn CN106248965A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610629366.4A Withdrawn CN106199009A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610629215.9A Withdrawn CN106248966A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201510723711.6A Active CN105334327B (en) | 2015-11-01 | 2015-11-01 | Kit and method for detecting ophthalmopathy |
CN201610628509.XA Withdrawn CN106199006A (en) | 2015-11-01 | 2015-11-01 | A kind of test kit for detecting oculopathy and detection method thereof |
CN201610628510.2A Withdrawn CN105974137A (en) | 2015-11-01 | 2015-11-01 | Kit for detecting eye diseases and detection method of kit |
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CN101144814A (en) * | 2007-10-22 | 2008-03-19 | 中国人民解放军第三军医大学第一附属医院 | Method for detecting, identifying and/ or quantifying compound using adapter type reagent |
CN104818278A (en) * | 2015-04-17 | 2015-08-05 | 刘红卫 | Aptamer capable of being in specific binding to TS/MDEP protein in gastric cancer cells |
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CN106199009A (en) | 2016-12-07 |
CN105334327A (en) | 2016-02-17 |
CN106018834A (en) | 2016-10-12 |
CN106248964A (en) | 2016-12-21 |
CN105974137A (en) | 2016-09-28 |
CN105334327B (en) | 2017-03-22 |
CN105974138A (en) | 2016-09-28 |
CN106018835A (en) | 2016-10-12 |
CN105974139A (en) | 2016-09-28 |
CN106199006A (en) | 2016-12-07 |
CN106248965A (en) | 2016-12-21 |
CN106018836A (en) | 2016-10-12 |
CN106248966A (en) | 2016-12-21 |
CN106199008A (en) | 2016-12-07 |
CN105974140A (en) | 2016-09-28 |
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Application publication date: 20161026 |