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Mirna to Evaluate Silence Delivery Technologies for microRNA Drug Candidates


By Doug Macron

Silence Therapeutics this week announced that it has signed a deal under which Mirna Therapeutics will evaluate two of its proprietary delivery technologies for use with Mirna's therapeutic microRNA mimics.

The agreement marks the second such deal in as many months for Silence as it works to leverage its technologies for applications outside of its core RNAi drugs focus.

Terms of the latest deal call for Mirna to provide Silence with specific undisclosed miRNA sequences that Silence will formulate with its AtuPlex and DBTC delivery systems.

The AtuPlex system, which targets the endothelium, is the cornerstone of Silence's stable of delivery agents. It comprises novel cationic lipid components that embed siRNA into multiple bi-layer structures, according to the company. The resultant nanoparticle consists of an siRNA payload, a cationic lipid, a fusiogenic lipid, and polyethylene glycol.

Notably, Silence is using the technology in its phase I siRNA-based cancer drug Atu-027.

The newer DBTC technology, meantime, is based on the same cationic lipid used in AtuPlex molecules, but is designed to be delivered specifically into hepatocytes and other liver cells.

Mirna will conduct in vitro and in vivo testing of the formulated miRNA sequences, and select lead candidates for further evaluation. Silence CEO Thomas Christely said that any licensing arrangement for the delivery technologies would be subject to additional agreements.

Financial terms of the deal were not disclosed.

For Mirna, the deal represents another step in its ongoing effort to select a delivery approach for its miRNA drug candidates. The company has a number of sequences that it aims to advance into the clinic, including its lead drug candidate miR-34 as a treatment for prostate cancer and other solid tumors, but had yet to determine just how they would be administered.

In August, Mirna President and CEO Paul Lammers told Gene Silencing News that the company was considering using a neutral lipid-emulsion it had developed in house, but found this approach needed additional work before being used in human trials (GSN 8/25/2011).

As such, the firm decided that a technology licensed from another company would be used with its first clinical candidate, and potentially other products. It seems Silence's technologies could fit that bill.

This week, Lammers confirmed that Mirna aims to move its miR-34 mimic into phase I development in early 2013.

For Silence, the deal with Mirna represents another effort to monetize its delivery expertise beyond its own drug programs.

Last month, the company announced that it had inked a deal to examine whether AtuPlex can be used to deliver miRNA mimics from InteRNA Technologies (GSN 9/15/2011).

Unlike the Mirna arrangement, however, this collaboration calls for both firms to conduct experiments on the drug candidates and select leads for further evaluation.

According to Christely, though the majority of Silence's expertise is with siRNA delivery, it is “confident” that its technologies can also be applied to single-stranded oligos such as miRNA mimics, in part because of its experience with antisense early in its history.

“In principle, they should work with all types of oligonucleotide therapeutics,” he said.

Christely also indicated that Silence would be open to the possibility of playing a more significant role in its collaborations with miRNA partners, though it would “depend on the partner.

“If they convince us that they have the right microRNAs, we are always prepared to look at any type of collaboration,” he said.

Still, “at the moment … we focus on siRNA therapeutics; that is where we have most of our knowledge,” Christely said. “But it doesn't hurt to [explore] further applications of these” delivery technologies in other areas should the deal be right.

Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com

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