Marina Biotech announces significant knockdown of gene targets in tumours with microRNA mimetic
Marina Biotech, Inc., a leading RNA-based drug discovery and development company, reported results from in vivo studies in rodent cancer models focused on effective delivery of a microRNA (miRNA) mimetic using Marina Biotech's proprietary Di-Alkylated Amino Acid (DiLA2) delivery system. Organ and tumour distribution studies demonstrated up to a 100-fold increase in miRNA copies per tumour cell as compared to baseline levels. Similar increases in the miRNA levels were noted in liver, lung, and heart after systemic administration of the mimetic formulated in DiLA2-based liposomes. Moreover, delivery of the miRNA mimetic in DiLA2 liposomes demonstrated approximately 60 per cent knockdown of mRNA for two genes whose down-regulation is the intended target of the miRNA mimetic.
"These data highlight the significant breadth in the potential uses of Marina Biotech's DiLA2 delivery system for RNA-based therapeutics," said J. Michael French, President and CEO of Marina Biotech at the Rodman & Renshaw 12th Annual Healthcare Conference in New York City. "The results support our plans to expand our therapeutic reach beyond our proprietary UsiRNA-based therapies to include both microRNA mimetics and antagomirs. Our broad delivery capability which includes both the DiLA2 and SMARTICLES technologies combined with our conformationally-restricted nucleotide (CRN) technology for stabilizing single-stranded oligonucleotides, creates a formidable drug discovery engine for the development of miRNA-based therapeutics."
"These experiments further demonstrate the flexibility of our DiLA2-based delivery technology for systemic administration," stated Barry Polisky, Ph.D., chief scientific officer of Marina Biotech, Inc. "The DiLA2 delivery system is capable of efficiently delivering small RNAs into cells and releasing their cargo to affect miRNA-mediated pathways, or siRNA-mediated knockdown, of a gene target. This is very exciting in the context of our ongoing efforts to develop RNA-based molecules that regulate the protein production of specific therapeutic targets involved in a host of diseases, including cancer."
Effective delivery is a well-recognized challenge in the development of RNA-based therapeutics. The versatility of the DiLA2 system provides for a rapid and scientifically robust process for improving the delivery characteristics of novel formulations to meet specific requirements of a particular therapeutic application, i.e., systemic administration for delivery to liver hepatocytes or local delivery to cells, such as the lung epithelium.
DiLA2 is Marina Biotech's proprietary delivery platform of novel synthetic di-alkylated amino acid compounds used to make liposomal delivery formulations. The DiLA2 platform enables Marina Biotech to tailor the charge, linker and acyl chains of amino acids in order to configure liposomes for delivery to target tissues of interest. In addition, the platform is designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics.
CRNs (Conformationally Restricted Nucleotides) are novel nucleoside analogs in which the flexible ribose sugar is locked into a rigid conformation by a small chemical linker, providing stability to oligonucleotides, and the opportunity to tailor on a position-by-position basis the specificity of a nucleic-acid based therapeutic or diagnostic.
Marina Biotech (formerly known as MDRNA, Inc.) is a biotechnology company focused on the development and commercialization of therapeutic products based on RNA interference (RNAi).