MDRNA, Inc., a leading RNAi-based drug discovery and development company, announced that it has acquired intellectual property for bridged nucleic acids from Valeant Pharmaceuticals North America. Bridged nucleic acids (BNA) are novel nucleoside analogs in which the flexible ribose sugar is locked into a rigid conformation by a small chemical linker. When included in single or double stranded oligonucleotides, the highly stable A-form of RNA or DNA is favoured, resulting in increased thermal stability of a duplex or higher affinity of a single strand for its complementary target, e.g., messenger RNA. In addition BNAs provide resistance to nuclease degradation.
"The BNA technology provides MDRNA a unique position in the development of RNA therapeutics," stated Barry Polisky, chief scientific officer of MDRNA. "BNA is highly complementary to our proprietary unlocked nucleobase analog (UNA) technology and enables MDRNA to tailor key characteristics of our UsiRNA constructs to impart greater versatility and specificity. Additionally, BNA strengthens MDRNA's proprietary meroduplex constructs and are directly applicable to alternative oligonucleotide constructs including single strand molecules and constructs which function outside of an RNAi mechanism."
The patent estate offers MDRNA considerable breadth in the research and development of nucleic acid-based therapies to include not only those with an RNAi mechanism of action, such as siRNA and miRNA, but those that function to inhibit RNA by a diverse set of mechanisms.
"We are focused on becoming the preeminent RNAi-based therapeutics company," stated J. Michael French, president and CEO of MDRNA. "The addition of this key intellectual property places us in a position to provide a broader array of RNAi-based drug discovery technologies to potential pharmaceutical partners and allows us entry into an important emerging therapeutic space driven by single stranded RNA constructs."
With the addition the of the BNA patent estate, MDRNA owns or controls 15 issued or allowed patents, and has 37 pending patent applications, 126 pending foreign patent applications and 7 PCT applications.
UsiRNAs are MDRNA's proprietary constructs in which Unlocked Nucleobase Analogs (UNA) strategically replace ribonucleotides, and are distinct from standard siRNAs. Placement of UNA in the passenger strand specifically blocks the activity of this strand to function in RNAi, thus decreasing off-target potential. Placement of UNA within the guide strand confers greater specificity upon RNAi by inhibiting micro-RNA-like effects. UsiRNAs have been demonstrated to be highly active in models of metabolic disorders and cancer, and function by RNAi to cleave their mRNA target.
MDRNA has shown that siRNAs containing a nick or gap in the passenger strand can be extremely active in RNAi. MDRNA has called these proprietary constructs "meroduplexes" to highlight the segmented nature of the duplex. These constructs eliminate off-target potential of the passenger strand by preventing its loading into RISC, while maintaining full potency and RNAi mechanism of action for the guide strand. Greater structural flexibility of the duplex, as imparted by the nicked passenger strand, results in decreased potential for cytokine induction associated with standard siRNAs.