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Accelerating target deconvolution for therapeutic antibody candidates using highly parallelized genome editing
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- Mattsson, Jenny (author)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,BioInvent International AB
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- Ekdahl, Ludvig (author)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Junghus, Fredrik (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- (creator_code:org_t)
- 2021-02-24
- 2021
- English.
- In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-8
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Therapeutic antibodies are transforming the treatment of cancer and autoimmune diseases. Today, a key challenge is finding antibodies against new targets. Phenotypic discovery promises to achieve this by enabling discovery of antibodies with therapeutic potential without specifying the molecular target a priori. Yet, deconvoluting the targets of phenotypically discovered antibodies remains a bottleneck; efficient deconvolution methods are needed for phenotypic discovery to reach its full potential. Here, we report a comprehensive investigation of a target deconvolution approach based on pooled CRISPR/Cas9. Applying this approach within three real-world phenotypic discovery programs, we rapidly deconvolute the targets of 38 of 39 test antibodies (97%), a success rate far higher than with existing approaches. Moreover, the approach scales well, requires much less work, and robustly identifies antibodies against the major histocompatibility complex. Our data establish CRISPR/Cas9 as a highly efficient target deconvolution approach, with immediate implications for the development of antibody-based drugs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
Keyword
- Antibodies/metabolism
- CRISPR-Cas Systems/genetics
- Cell Line, Tumor
- Cell Survival/genetics
- Clustered Regularly Interspaced Short Palindromic Repeats/genetics
- Gene Editing
- Humans
Publication and Content Type
- art (subject category)
- ref (subject category)
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- Mattsson, Jenny
- Ekdahl, Ludvig
- Junghus, Fredrik
- Ajore, Ram
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- Frendéus, Björn
- Teige, Ingrid
- Nilsson, Björn
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