In 2007, the science of RNAi continued to march forward with innovations in delivery, advances in addressing off-target effects, greater use of large-scale screens, and the increase in RNAi-based drugs moving into human testing.
But it was the work done with small, non-coding RNA such as microRNA that topped many industry insiders’ lists of key achievements for the year.
According to John Rossi, a City of Hope researcher and co-founder of RNAi drug companies Calando Pharmaceuticals and Dicerna, “microRNAs continue to be an explosive area of new understanding. The fact of the matter is that they are so important that we can’t ignore them,” he notes.
In 2007, research linking miRNA to a host of biological processes and disease states — including cancer and cardiovascular health — continued to grow, adding to the body of evidence indicating that these small RNA will prove to be major players in the diagnostic and therapeutic arenas.
At the same time, a distinct class of small, regulatory RNA — Piwi-interacting RNA — have landed firmly on the radar screens of the same people who helped make RNAi the subject of Nobel Prize-winning research.
Since little is known about piRNA, “for now [they comprise] a parallel universe” to RNAi, says Phil Zamore, Alnylam Pharmaceuticals co-founder and University of Massachusetts Medical School researcher. “But I’m keeping an open mind,” he adds. “The [RNAi] field emerged from work done by people who had open minds, which [can be] relatively rare in science, and were willing to say that weird stuff was real and interesting and had biological explanations.”
To Zamore, “the [Julius] Brennecke Cell paper was the highlight of the year.” In that paper, Brennecke and colleagues from Cold Spring Harbor Laboratory reported that piRNA act as “master regulators” of transposon activity in Drosophila.
Nastech Pharmaceutical transferred its RNAi intellectual property, including patent applications related to RNA-based drugs and diagnostics, to MDRNA, a spinout that will develop therapeutics based on the gene-silencing technology.
Rosetta Genomics chose Nanogen’s MGB probes as the platform for its microRNA-based diagnostics. Under the license, Rosetta will be able to create a line of real-time PCR diagnostics based on the small, non-coding RNA.
RXi Pharmaceuticals licensed RNAi sequences for specific target genes from Thermo Fisher Scientific. The genes are related to type 2 diabetes, neurology, obesity, and oncology.
Cell Genesys sold its lentiviral gene-delivery system to GBP Capital, which is the majority shareholder of gene-delivery firm Lentigen, for $12 million.
A recessive genetic screen to elucidate RNA silencing in embryonic stem cells
Grantee: Xiaozhong Wang, Northwestern University
Began: Feb. 1, 2007; Ends: Jan. 31, 2009
Wang received $188,750 to develop new ways to genetically analyze embryonic stem cells. His lab developed a recessive genetic screen to identify components of the mammalian RNAi pathway and he now plans to use that on a large scale to screen for RNAi mutants. His team will study novel areas of the vertebrate genome using recessive genetic screens to study genetic pathways.
RNAi as a modulator of arbovirus vector competence in transgenic Aedes aegypti
Grantee: Alexander Franz, Colorado State University
Began: Sept. 30, 2007; Ends: Aug. 31, 2011
Franz was awarded $294,000 to study the interactions of the mosquito, Aedes aegypti, with the viruses it may transmit. Flaviviruses and alphaviruses are targets of RNAi when in the mosquito gut and Franz’s lab hypothesizes that RNAi is an innate immune response to viruses in the mosquito gut. They will be manipulating the gut RNAi pathway of transgenic mosquitoes.