With delivery remaining the key problem facing the successful development of RNAi therapeutics, an increasing number of players in the field are looking within their own labs for solutions, often using delivery technologies as the foundation upon which to build their businesses.
Although the need for effective delivery approaches has long been recognized, many of the early entrants into the RNAi therapeutics space — companies such as Alnylam Pharmaceuticals, Sirna Therapeutics (now a part of Merck), Atugen (now Silence Therapeutics), and CytRx (which spun out its RNAi drug operations into RXi Pharmaceuticals) — focused much of their initial research and development on the molecules themselves.
But with a greater understanding of how to design and modify functional siRNAs and licenses to key intellectual property now widely available, many RNAi drug firms are making delivery their first priority.
Topping the list is Tekmira Pharmaceuticals, which secured access to one of the RNAi drug field's most important delivery technologies when it merged with Protiva Biotherapeutics about a year ago.
That technology, termed SNALPs, or stable nucleic acid lipid particles, was developed by Protiva and comprises nucleic acids encapsulated by cationic and fusogenic lipids surrounded by a polyethylene glycol coating to prevent the positively charged cationic lipid from clearing the bloodstream.
The technology proved so promising that both Alnylam and Sirna took early licenses, although a lawsuit between Protiva and Tekmira predecessor Inex Pharmaceuticals ultimately led to a restructuring of the arrangement with Sirna. Alnylam, however, continues to use the technology.
The litigation was settled through the Tekmira/Protiva merger, and Tekmira has since attracted a number of additional companies interested in using SNALPs in their own RNAi efforts, including Roche, Johnson & Johnson, and Bristol-Myers Squibb.
With revenues from these and other collaborations, Tekmira has been able to fund its own siRNA drug pipeline.
Amount Novartis paid for 65,922 unregistered shares of Alnylam Pharmaceuticals.
Alnylam Pharmaceuticals and Isis Pharmaceuticals have formed a collaboration to develop Isis' single-stranded RNAi technology. Alnylam received a co-exclusive license to Isis' ssRNAi technology, in exchange for which Isis
will receive upfront payments, research and development milestones, and royalties.
Rosetta Genomics closed a deal with Prometheus Laboratories that gives Prometheus the US market rights to Rosetta's three microRNA-based diagnostics: miRview Meso, miRview Mets, and miRview Squamous.
The US Food and Drug Administration approved Tekmira Pharmaceuticals' investigational new drug application for ApoB SNALP, a siRNA-based hypercholesterolemia drug that targets apolipoprotein B.
Double-stranded RNA-mediated signaling pathway and gene silencing
Grantee: Yi Liu, University of Texas Southwest Medical Center
Began: Apr. 1, 2009; Ends: Mar. 31, 2011
For this grant Yi Liu will be studying the signaling pathway responsible for dsRNA-induced gene transcription in the filamentous fungus Neurospora crassa through forward and reverse genetics. They will also investigate the biogenesis and function of DNA damage-induced small RNAs and the mechanism of aberrant RNA production after that damage.
Role of RNA Silencing in Telomere Dynamics
Grantee: Zhixin Xie, Texas Tech University
Began: May 1, 2009; Ends: Apr. 30, 2012
Zhixin Xie plans to use both genetic and biochemical approaches to elucidate the role of RNA silencing in telomere dynamics. He will investigate the origin and mechanism of tel-siRNAs and determine tel-siRNAs' part in telomere dynamics by using the tel-siRNA deficient mutants. He also plans to characterize the tel-siRNA-associated effector complex.