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Procaryotic cell in vivo antibody library construction screening and optimizing of antibody and use

An antibody library, prokaryotic cell technology, applied in the direction of antibodies, chemical instruments and methods, biochemical equipment and methods, etc., can solve the problems of difficult operation and slow growth of yeast, and achieve the effect of high affinity and high specificity

Inactive Publication Date: 2003-04-09
韩泽广
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But yeast grows slowly and is not easy to operate
At present, phage display technology is mainly introduced in China to establish human high-titer libraries, and no other methods have been used.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: Embodiment 1 is to further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention (the same applies to the following embodiments). The method for constructing an antibody library in a prokaryotic cell comprises the following steps: (1) taking immune-related tissues and cells such as peripheral blood, lymph nodes, spleen, bone marrow, and liver of organisms; (2) isolating RNA from the taken tissues and cells, and Reverse transcription to obtain cDNA; (3) Design DNA primers for the variable region of the heavy chain of the immunoglobulin, the variable region of the light chain and the third constant region respectively, and amplify the variable region of the heavy chain of the immunoglobulin, the variable region of the heavy chain and the third constant region of the obtained cDNA. light chain variable region and the third...

Embodiment 2

[0041]Embodiment 2: the method for screening specific antibody in prokaryotic cells, comprising the following steps:

[0042] (1) The full-length or partial open reading frame (ORF) of the antigen gene is inserted into the DNA sequence that can be used as a bait plasmid in bacterial two-hybrid. Bait plasmids include all plasmids that can be used in prokaryotic cells, that is, bacterial two-hybrids. In addition to the common protein-coding genes of general plasmids, this plasmid also contains partial sequences of special protein-coding genes such as DNA-binding proteins or adenylyl cyclase. . The inserted antigen gene can form a fusion gene with the DNA-binding protein sequence or the partial sequence of adenylyl cyclase. (2) The plasmid containing the antigen obtained from step (1) is mixed with the plasmid containing the antibody library obtained from the library construction step (4), and the plasmid containing the reporter gene (such as antibiotic resistance gene and β-gal...

Embodiment 3

[0043] Example 3: A method for constructing a secondary antibody library in prokaryotic cells, comprising the following steps: (1) Using the original antibody light chain and heavy chain variable region as a template, the following method is used to construct a derived secondary antibody library, but Not limited to the following 4 methods. The light chain and heavy chain variable regions were amplified by random mutagenesis of polymerase chain reaction (PCR), inserted into the above-mentioned plasmids used to construct antibody libraries, and combined with specific protein-coding genes in the plasmids such as RNA polymerase α subunit or The partial sequence of adenylate cyclase forms a fusion gene to form a secondary antibody library; (2) After inserting the original antibody light chain and heavy chain variable regions into the above-mentioned plasmids used to construct the antibody library, use special host bacteria Cause random mutations, extract plasmids, and form a second...

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PUM

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Abstract

Inside prokaryotic cell or colibacillus, special recombinant palsmid capable of proliferating and expressing and being used in double cross of colibacillus is used to construct library of various antibody, antibody segment and second antibody. Before the antibody is screened, the antigen is not purified and the DNA sequence containing antigen epitope gene and partial or whole open reading frame form with fusion protein together with specially encoded gene for the screening and optimizing of antigen with high specificity and high affinity. The antibody and antibody segment may be used as medicine for clincial diagnosis and treatmand as well as in life science research, production and improvement of antibody engineering and gene engineering.

Description

1. Technical field [0001] The present invention relates to the fields of genomics, proteomics, molecular biology, immunology, cell biology, antibody engineering, genetic engineering and clinical medicine such as disease treatment and diagnosis. Construction of multi-genus, high-titer, high-abundance, high-diversity antibody libraries, screening and optimization of high-specificity, high-affinity antibodies and their use. 2. Background technology [0002] There are many methods used in the past to generate antibodies. Such as injecting antigens into animals such as rabbits to produce polyclonal antibodies, or immunizing animals such as mice in combination with hybridoma technology to prepare monoclonal antibodies (for example, Kohler et al., Nature 256:495, 1975; Kohler et al., Eur. J. Immunol. 6:511, 1976; Kohler et al., Eur. J. Immunol. 6:292, 1976). However, none of the above is a multi-genus, high-titer, high-abundance, and high-diversity antibody library, and the antib...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395C07K16/00C12N15/70C12P21/02C12Q1/68G01N33/68
Inventor 韩泽广刘锋张新段煜
Owner 韩泽广