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British-Swedish drugmaker AstraZeneca has partnered with US-based Isis Pharmaceuticals to develop new delivery methods for antisense oligonucleotides.

According to Isis, new methods are being developed to target the desired tissue more effectively.

Antisense oligonucleotides are short and single strands of DNA or ribonucleic acid (RNA) molecules, which act before proteins are produced at the level of messenger RNA in the cell, and open new opportunities for therapeutic intervention.

The new agreement was based on the existing deal made in 2012 for oncology, and later expanded in 2013 to include cardiovascular and metabolic diseases (CVMD).

AstraZeneca oncology innovative medicines unit head Susan Galbraith said: "This exciting collaboration very much supports AstraZeneca’s research and development in the area of RNA-based therapeutics.

"If successful, we’ll have a way to selectivity modulate therapeutic targets in specific cell types that are intractable to small molecules and antibodies."

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"Antisense oligonucleotides are short and single strands of DNA or ribonucleic acid (RNA) molecules, which act before proteins are produced at the level of messenger RNA in the cell, and open new opportunities for therapeutic intervention."

Building on Isis’s Ligand Conjugation Antisense (LICA) technology, the new delivery methods will be designed to enhance the access of antisense oligonucleotides into specific organs and cells.

Each company will fund its own contribution and commit investigators to the collaboration. The firms will work together on an agreed programme and share rights to the results, in line with AstraZeneca’s open innovation approach.

Isis intends to use learnings from this collaboration across its antisense technology platform, while AstraZeneca plans to apply across its RNA-based, small molecule and antibody research and development activities.

One of the molecules being developed is AZD9150 (ISIS-STAT3Rx), under the 2012 agreement. It is the first-in-human antisense oligonucleotide inhibitor of STAT3 that is being developed as an immunomodulatory agent in combination with MEDI4736.

Isis noted that second product of the collaboration is an antisense oncology compound targeting the androgen receptor AZD5312 (ISIS-ARRx) and is in Phase I trials.


Image: AstraZeneca’s R&D Site in Mölndal, Sweden. Photo: courtesy of Erik031.