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May 28, 2009
 |  BC Innovations  |  Targets & Mechanisms

New angiogenesis targets

An international collaboration among researchers at the Karolinska Institute, Discovery Genomics Inc. and AngioGenetics AB has produced a set of previously unknown and potentially druggable targets in angiogenesis along with several matching antiangiogenic compounds.1

AngioGenetics was acquired by BioInvent International AB in 2007, and BioInvent now holds joint IP rights to the discoveries along with Discovery Genomics. The discoveries are the result of a 2002 partnership between AngioGenetics and Discovery Genomics.

The study, which combined a genetic screen with a chemical one, was published in Chemistry & Biology and was led by Mats Hellström, senior scientist at Karolinska and senior principal scientist at BioInvent.

Although genetic and pharmacological screens for angiogenesis targets have been done before, Hellström said the team's effort is the first to combine the two approaches to link compounds to targets.

"To identify new angiogenesis targets, we created a cDNA library of endothelial genes and screened for their effect in zebrafish," said Hellström. "We then screened compound libraries for effects on those pathways."

The team initially used microarrays to identify cDNAs expressed in mouse vascular tissue.From an initial count of 150, the researchers winnowed the list down to 50 druggable candidate genes that were also present in zebrafish. The team then knocked down the expression of these genes in zebrafish embryos using morpholinos, a type of antisense molecule, and looked for...

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