By Doug Macron
Boston Biomedical was awarded last month a one-year, $312,194 grant from the National Institutes of Health to develop its so-called asymmetric interfering RNA technology for research applications.
The company plans to use the funding to optimize the design of the aiRNA oligos as reagents for “gene function research, including genome-wide genomics studies,” the grant's abstract states.
AiRNAs are essentially 15-nucleotide long, asymmetric RNA duplexes with 3’ and 5’ antisense overhangs. In a paper published in Nature Biotechnology in late 2008, Boston Biomedical founder and CEO Chiang Li and colleagues reported that the constructs were incorporated into RISC and mediated sequence-specific target mRNA cleavage through the RNAi pathway in vitro.
Around that time, Li told Gene Silencing News that the aiRNA technology offered a means of operating around the intellectual property estates of other companies in the RNAi space, namely Alnylam Pharmaceuticals and Merck's Sirna Therapeutics, that cover traditional 19 to 21 nucleotide-long siRNAs (GSN 12/11/2008).
According to the grant's abstract, the aiRNA technology may also offer a means of sidestepping some of the limitations associated with siRNAs, which are “plagued by variable gene silencing effects, the activation of innate immune responses, and the knockdown of non-targeted mRNA.
“These well-recognized effects complicate the interpretation of gene function experiments that rely on specific target gene knockdown,” the abstract notes. “Moreover, these problems can become impossible to manage in large-scale functional genomics experiments that test gene function in vivo.”
In contrast, aiRNAs have been shown to be “highly efficient” in mammalian cells and eliminate sense-strand off-target silencing while “significantly” reducing interferon response induction, the abstract adds. In their Nature Biotechnology paper, the Boston Biomedical team speculated that this may be in part due to the oligos' asymmetrical structure, which preferentially loads the antisense strand into RISC.
Viewing the technology as holding “significant potential for broad applications in biological research,” the company plans to “examine various aiRNA structures to determine the best design for inducing potent and highly specific silencing under various experimental conditions,” the abstract states. It will also evaluate existing siRNA design algorithms for clues to design efficacious aiRNA oligos, and identify “key elements for the development of an aiRNA-specific design algorithm.”
Follow-on work will include the construction of a library of optimized aiRNA structures targeting “all known human genes,” the abstract adds. “The ability of the aiRNA library to mediate efficacious and specific gene silencing in vitro will then be evaluated.”
The further development of aiRNA technology should significantly improve our ability to analyze gene function, and may have significant implications for other applications involving RNAi-mediated gene silencing, the abstract adds.
The grant began on May 1 and runs until the end of April 2012.
AiRNA No More?
Shortly after Boston Biomedical published the aiRNA data in 2008, the company announced that it had founded a new firm, called AiRNA Pharmaceuticals, to develop the technology for therapeutic applications (GSN 12/11/2008).
At the time, Li said that the constructs' unique shape would be a key selling point to potential partners, and predicted at least one collaboration in the near term. At the same time, AiRNA was expected to have selected a drug candidate and filed with US regulators by late 2009.
However, it appears that AiRNA failed to hit either of those targets, and it remains unclear whether the company is still in operation. AiRNA's website is not functional, and officials from Boston Biomedical did not return a request for comment.
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