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Arrowhead Publishes Data on Advances in Subcutaneous siRNA Delivery
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Arrowhead Publishes Data on Advances in Subcutaneous siRNA Delivery

Arrowhead Publishes Data on Advances in Subcutaneous siRNA Delivery
News

Arrowhead Publishes Data on Advances in Subcutaneous siRNA Delivery

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Arrowhead Research Corporation a biopharmaceutical company developing targeted RNAi therapeutics, today announced the publication of new data on a subcutaneously administered formulation of its Dynamic Polyconjugate delivery system. This new class of DPCs may also enable targeting of RNAi therapeutics to tissues outside of the liver. The manuscript entitled, “Protease-triggered siRNA delivery vehicles,” by David B. Rozema et al, was made available online ahead of print in the Journal of Controlled Release 209 (2015) 57-66.

In the publication, Arrowhead scientists describe the development of protease-sensitive masking chemistries that are used in a class DPCs where the RNAi trigger molecule is conjugated directly to the polymer delivery vehicle. These new vehicles expand on the company’s existing acid labile DPCs, where the polymer and RNAi trigger are two separate molecules and are co-injected. The protease-sensitive linkages appear to be more stable and have longer circulation times, which may allow for an increased range of targeting, and appear amenable to subcutaneous administration. The publication reports a high level of target gene knockdown and long duration of effect can be achieved after subcutaneous injection with these new DPC delivery vehicles in nonhuman primates. After a single subcutaneous injection of 0.5 mg/kg siRNA against Factor 7 (FVII), a liver expressed coagulation factor that is secreted into the bloodstream, a 99% reduction of FVII activity was observed in nonhuman primates. Further, this reduction was highly durable with maximal knockdown occurring 24 days after injection and measurable reduction in FVII activity appears to persist for up to 200 days.

"This publication speaks to the flexibility of the DPCs and the ability of our scientists to continually expand the platform to enable additional uses,” said Christopher Anzalone, Ph.D., president and chief executive officer. “These data suggest that subcutaneously administered DPCs that employ the protease sensitive masking chemistries may be well suited to address chronic diseases of the liver that require long-term treatment and where long dosing intervals would be very attractive to physicians and patients.”


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