Gregory Hannon has developed research tools based on an evolutionarily conserved mechanism for gene silencing called RNA interference (RNAi). As a leader in the RNAi field, Dr. Hannon has uncovered how the process operates in mammalian cells and has exploited this biology to manipulate gene expression. Dr Hannon constructed vectors that can be introduced into mammalian cells or tissues and by expressing an interfering RNA molecule (a ‘short hairpin RNA’), can selectively shut down expression of the complementary gene. Dr. Hannon generated a library of vectors expressing silencing RNA's directed against all human genes. This library represents a set of reagents that will allow investigators to shut down, one-by-one, every gene in the human genome. Based on the increased understanding of the biochemistry of the RNA interference, Dr. Hannon designed second-generation short hairpin RNA expression libraries with improved activity. These libraries comprise 140,000 short hairpin RNA expression plasmids, covering a substantial fraction of all predicted genes in the human and mouse genomes. These libraries are available to the scientific community.
The libraries are proving to be a valuable tool for understanding gene function, identification of potential therapeutic drug targets and generation of animal models. Working with Dr. Hannon, Scott Lowe’s laboratory showed that the second generation shRNAs were able to stably and reversibly manipulate gene expression in animals.