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Journal ArticleDOI

CDR Walking Mutagenesis for the Affinity Maturation of a Potent Human Anti-HIV-1 Antibody into the Picomolar Range

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TLDR
The methodology presented here provides a route for the improvement of the affinities of antibodies typical of tertiary immune responses into the picomolar range and may have profound effects on the utility of antibodies as therapeutic and prophylactic agents.
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This article is published in Journal of Molecular Biology.The article was published on 1995-12-01. It has received 578 citations till now. The article focuses on the topics: Affinity maturation & Phage display.

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Citations
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In vitro selection and evolution of functional proteins by using ribosome display.

TL;DR: Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.
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Potent antibody therapeutics by design

TL;DR: The generation of potent antibody therapeutics, which I review here, is an iterative design process that involves the generation and optimization of antibodies to improve their clinical potential.
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Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen.

TL;DR: The final antibody has improved affinity for several VEGF variants as compared with the parental antibody; however, some contact residues on V EGF differ in their contribution to the energetics of Fab binding.
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Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides.

TL;DR: The small number of 49 master genes will allow future improvements to be incorporated quickly, and the separation of the frameworks may help in analyzing why nature has evolved these distinct subfamilies of antibody germline genes.
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Selecting and screening recombinant antibody libraries

TL;DR: The first antibody of this new generation, adalimumab (Humira, a human IgG1 specific for human tumor necrosis factor (TNF)), already approved for therapy and with many more in clinical trials, these recombinant antibody technologies will provide a solid basis for the discovery of antibody-based biopharmaceuticals, diagnostics and research reagents for decades to come.
References
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Journal ArticleDOI

Assembly of combinatorial antibody libraries on phage surfaces: the gene III site.

TL;DR: A phagemid system was developed for the monovalent display of combinatorial antibody Fab libraries on the surface of filamentous phage M13, and may replace current antibody cloning techniques.
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Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody

TL;DR: A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization, implying the conservation of a structural feature on gp120, which could be important in vaccine design.
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