Marina Biotech Publishes Pre-Clinical Research on the Application of DiLA2 Delivery Technology for Systemic Delivery of siRNAs
News Apr 28, 2011
Marina Biotech, Inc. has announced the publication of data highlighting the application of their proprietary DiLA2-based delivery technology for systemic administration of siRNAs; this work is described in Molecular Therapy - a Nature publication.
The manuscript, titled "An Amino Acid-based Amphoteric Liposomal Delivery System for Systemic Administration of siRNA" (Adami et al. Molecular Therapy advance online publication 19 April 2011 doi: 10.1038/mt.2011.56; http://www.nature.com/mt/index.html) describes the development of an amphoteric DiLA2 delivery system which enabled efficient knockdown of multiple targets in liver.
Marina Biotech has recently entered an exclusive agreement with Debiopharm Group for the development and commercialization of the Company's bladder cancer program which utilizes a DiLA2-based delivery technology.
"We're pleased to be able to publish these exciting results," stated Barry Polisky, PhD, Chief Scientific Officer at Marina Biotech Inc.
Polisky continued, "Delivery remains one of the key challenges in advancing RNAi-based therapeutics into the clinic and the publication of this paper highlights the impact of our DiLA2 technology in demonstrating safe and efficient systemic delivery of siRNAs. Thus far, the chemical space screened in this manuscript represents a relatively small percentage of the DiLA2 compounds that can be evaluated. The DiLA2 platform provides for a vast and chemically diverse library of compounds that can be tailored to meet particular siRNA delivery objectives for the treatment of various diseases. We will continue to develop our understanding of the capabilities of this novel delivery technology."
One of the DiLA2-based delivery formulations, an amphoteric formulation, when administered systemically, resulted in greater than 80% knockdown of ApoB, TTR, Factor VII and PCSK9 messenger RNA (mRNA) with a single 2 mg/kg dose. The ED50 values for knockdown of these mRNAs ranged from 0.1 to 0.25 mg/kg.
The formulation was well tolerated with single and multiple dose regimens. Additionally when stored frozen, DiLA2-based formulations demonstrated physical and chemical stability for greater than one year, a necessary attribute for developing liposomal-based siRNA drug products.
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