Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection

Phage display technologies are powerful tools for selecting binding ligands against purified molecular targets, live cells, and organ vasculature. However, the selection of natural ligands using phage display has been limited because of significant problems associated with the display of complex cDN...

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Main Authors: Peggy Ho Faix, Michael A. Burg, Michelle Gonzales, Edward P. Ravey, Andrew Baird, David Larocca
Format: Article
Language:English
Published: Taylor & Francis Group 2004-06-01
Series:BioTechniques
Online Access:https://www.future-science.com/doi/10.2144/04366RR03
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author Peggy Ho Faix
Michael A. Burg
Michelle Gonzales
Edward P. Ravey
Andrew Baird
David Larocca
author_facet Peggy Ho Faix
Michael A. Burg
Michelle Gonzales
Edward P. Ravey
Andrew Baird
David Larocca
author_sort Peggy Ho Faix
collection DOAJ
description Phage display technologies are powerful tools for selecting binding ligands against purified molecular targets, live cells, and organ vasculature. However, the selection of natural ligands using phage display has been limited because of significant problems associated with the display of complex cDNA repertoires. Here we describe the use of cDNA fragmentation and open reading frame (ORF) selection to display a human placental cDNA library on the pIII coat protein of filamentous phage. The library was enriched for ORFs by selecting cDNA-β-lactamase fusion proteins on ampicillin, resulting in a cDNA population having 97% ORFs. The ORF-selected cDNAs were fused to pIII in the phagemid vector, pUCMG4CT-198, and the library was rescued with a pIII-deleted helper phage for multivalent display. The resulting phagemid particle library consisted of 87% ORFs, compared to only 6% ORFs when prepared without ORF selection. Western blot analysis indicated cDNA-pIII fusion protein expression in eight out of nine ORF clones tested, and seven of the ORF encoded peptides were displayed multivalently. The high level of cDNA expression obtained by ORF selection suggests that ORF-enriched phage cDNA libraries prepared by these methods will be useful as functional genomics tools for identifying natural ligands from various source tissues.
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spelling doaj-art-429f19afa5fb4bcfba85ab356418dac32025-08-20T02:26:07ZengTaylor & Francis GroupBioTechniques0736-62051940-98182004-06-013661018102910.2144/04366RR03Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selectionPeggy Ho Faix0Michael A. Burg1Michelle Gonzales2Edward P. Ravey3Andrew Baird4David Larocca51Selective Genetics, Inc., San Diego, CA, USA1Selective Genetics, Inc., San Diego, CA, USA1Selective Genetics, Inc., San Diego, CA, USA1Selective Genetics, Inc., San Diego, CA, USA2King's College London, London, UK1Selective Genetics, Inc., San Diego, CA, USAPhage display technologies are powerful tools for selecting binding ligands against purified molecular targets, live cells, and organ vasculature. However, the selection of natural ligands using phage display has been limited because of significant problems associated with the display of complex cDNA repertoires. Here we describe the use of cDNA fragmentation and open reading frame (ORF) selection to display a human placental cDNA library on the pIII coat protein of filamentous phage. The library was enriched for ORFs by selecting cDNA-β-lactamase fusion proteins on ampicillin, resulting in a cDNA population having 97% ORFs. The ORF-selected cDNAs were fused to pIII in the phagemid vector, pUCMG4CT-198, and the library was rescued with a pIII-deleted helper phage for multivalent display. The resulting phagemid particle library consisted of 87% ORFs, compared to only 6% ORFs when prepared without ORF selection. Western blot analysis indicated cDNA-pIII fusion protein expression in eight out of nine ORF clones tested, and seven of the ORF encoded peptides were displayed multivalently. The high level of cDNA expression obtained by ORF selection suggests that ORF-enriched phage cDNA libraries prepared by these methods will be useful as functional genomics tools for identifying natural ligands from various source tissues.https://www.future-science.com/doi/10.2144/04366RR03
spellingShingle Peggy Ho Faix
Michael A. Burg
Michelle Gonzales
Edward P. Ravey
Andrew Baird
David Larocca
Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
BioTechniques
title Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
title_full Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
title_fullStr Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
title_full_unstemmed Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
title_short Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection
title_sort phage display of cdna libraries enrichment of cdna expression using open reading frame selection
url https://www.future-science.com/doi/10.2144/04366RR03
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