Arrayed adenoviral expression libraries for functional screening

Frits Michiels, Helmuth van Es, Luc Van Rompaey, Pascal Merchiers, Bart Francken, Karen Pittois, Jan van der Schueren, Reginald Brys, Johan Vandersmissen, Filip Beirinckx, Sofie Herman, Kristina Dokic, Hugo Klaassen, Evi Narinx, Annick Hagers, Wendy Laenen, Ivo Piest, Heidi Pavliska, Yvonne Rombout, Ellen LangemeijerLibin Ma, Christel Schipper, Marc De Raeymaeker, Stephane Schweicher, Mia Jans, Kris Van Beeck, Ing Ren Tsang, Onno De Van Stolpe, Peter Tomme

Research output: Contribution to JournalArticleAcademicpeer-review


With the publication of the sequence of the human genome, we are challenged to identify the functions of an estimated 70, 000 human genes1.2 and the much larger number of proteins encoded by these genes. Of particular interest is the identification of gene products that play a role in human disease pathways, as these proteins include potential new targets that may lead to improved therapeutic strategies. This requires the direct measurement of gene function on a genomic scale in cell-based, functional assays. We have constructed and validated an individually arrayed, replication-defective adenoviral library harboring human cDNAs, termed PhenoSelect library. The adenoviral vector guarantees efficient transduction of diverse cell types, including primary cells. The arrayed format allows screening of this library in a variety of cellular assays in search for gene(s) that, by overexpression, induce a particular disease-related phenotype. The great majority of phenotypic assays, including morphological assays, can be screened with arrayed libraries. In contrast, pooled-library approaches often rely on phenotype-based isolation or selection of single cells by employing a flow cytometer or screening for cell survival. An arrayed placental PhenoSelect library was screened in cellular assays aimed at identifying regulators of osteogenesis, metastasis, and angiogenesis. This resulted in the identification of known regulators, as well as novel sequences that encode proteins hitherto not known to play a role in these pathways. These results establish the value of the PhenoSelect platform, in combination with cellular screens, for gene function discovery.

Original languageEnglish
Pages (from-to)1154-1157
Number of pages4
JournalNature Biotechnology
Issue number11
Publication statusPublished - 20 Nov 2002
Externally publishedYes


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