Since I know that many readers of this blog share a keen interest in Tekmira and the fate of SNALP delivery, one if not the leading systemic delivery technology for RNAi gene knockdown in the liver, and likely with use for solid cancers and immune-related diseases as well, you may like what I dug out today from the long-neglected junk mail pile on my desk: An abstract for the 6th Annual CHI conference on ‘RNAi for Therapeutics’ (Boston 22-23 October) by Pieter Peeters from the Johnson&Johnson company entitled ‘LIVER-SPECIFIC KNOCKDOWN USING SNALP-FORMULATED siRNAs TO STUDY PATHWAYS IN LIPOPROTEIN SECRETION AND STEATOSIS’.
The abstract body, which can also be found online here, as follows:
“As the application of RNA interference in vivo further develops, we are pursuing several promising technologies for systemic delivery. The goal of the current study was to evaluate the SNALP (“Stable Nucleic Acid Particles”) systemic RNAi delivery platform to knockdown genes encoding for key enzymes in triglyceride synthesis. SNALP-Formulated siRNAs were found to effectively knockdown mRNA levels by >90% in liver compared to a SNALP-Delivered scrambled siRNA control. The effect knock-down in liver was further investigated following a 3-week high-fat feeding challenge. The results demonstrated the efficient in vivo SNALP-mediated delivery of siRNA by systemic route and the utility of targeting novel targets to reduce fat storage in liver and improve hepatic steatosis.”
It is thus apparent that J&J is one of the as yet undisclosed SNALP evaluation partners of Tekmira, and has extensively used the delivery technology for target discovery/validation purposes as well as with a view of using it as a therapeutic modality itself. Given the obvious success of their efforts (note that J&J chose to present SNALP from among the other 'promising' delivery technologies it has evaluated), I would not be surprised for J&J to soon join the ranks of Alnylam, Merck, Takeda, Bristol-Myers Squibbs, and Roche, as the next major Tekmira SNALP RNAi delivery partner.
While I do not say that SNALP is the end-all, be-all for gene knockdown of the liver with new technologies likely to emerge over time, the extensive successful use of the technology by third-parties is great validation of its reproducibility and clinical relevance for advancement into the clinic at this time, and a testament to not just the liposomal patent position of Tekmira, but also the RNAi-related know-how of its scientists (see also Tekmira’s publication on the immunostimulatory potential of siRNAs and how to avoid it here).
Beyond the use of SNALP-RNAi in target validation, where will J&J likely be interested in applying the technology clinically? My first bet certainly would be on the treatment of hepatitis C infection. Not long ago, we learnt from a report in RNAiNews that J&J was about to contribute to a $25M fund-raising round for the DNA-directed RNAi company Nucleonics before the deal was called off on questions about scientific misconduct. I honestly could not believe that J&J would even consider collaborating with a company that has entered an RNAi phase I clinical trial for hepatitis B that was so patently destined to fail because of the known inefficiency of liposomal plasmid (not siRNA) delivery.
Developing an RNAi Therapeutic for HepC has also to be seen within the context of building upon J&J’s imminent franchise in this hard-fought market. Together with marketing and development partner Vertex Pharmaceuticals it is currently conducting phase III studies for telaprevir, a protease inhibitor that has all the looks of becoming the next big breakthrough drug in HepC (my other favorite biotech drug story is Tysabri, in case you wanted to know). With predicted cure rates of 60-70% for type I after the introduction of protease inhibitors, RNAi antivirals should be able to enhance cure rates due to their complementary mechanism of action.
Two years ago, J&J awarded RNAi discoverer and Nobel Laureate Craig Mello the Dr. Paul Janssen Award for Biomedical Research. This alone leads me to believe that J&J should have broad ambitions in RNAi as a platform technology. As the number of conference abstracts related to RNAi in the liver (especially fibrosis, metabolic disease) suggests, the liver alone should yield sufficient targets to keep SNALP scientists busy for now.
PS: Since I know that this blog is also read by some larger investment companies, despite the apparently low volume of Tekmira on the Toronto Stock Exchange, it should be possible to acquire shares in size without moving the price too much as the overhang of Protiva stock following the merger is noticeable. End of advertisement.
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