Marina Biotech this week announced that it has conducted experiments in which its conformationally restricted nucleotide technology was used to produce microRNA antagonists capable of de-repressing targets of miR-122 in vivo.
The agent could trigger two-and-a-half-fold de-repression of the miRNA's targets at a dose of 10 mg/kg, while demonstrating “good tolerability with repeat dosing,” the company said.
The CRN technology essentially comprises nucleotide analogs to which the C2' and C4' carbon bonds of the ribose ring are linked. Marina has been touting its utility in the creation of efficient miRNA inhibitors for some time (GSN 7/14/2011).
"With the completion of this early work with our CRN chemistry, we now have in vivo demonstration of our ability to develop single-stranded oligonucleotide therapeutic compounds," Marina President and CEO Michael French said in a statement. "Further, we now have in vivo proof of concept across our entire nucleic acid-based therapeutic platform demonstrating the ability to silence gene targets through either RNA interference or translational blocking, or via a microRNA mimetic, and, in the case of these data, to up-regulate gene targets via a microRNA antagonist.”