A novel platform to enable inhaled naked RNAi medicine for lung cancer.

Abstract

Small interfering RNA (siRNA)-based therapeutics have been used in humans and offer distinct advantages over traditional therapies. However, previous investigations have shown that there are several technical obstacles that need to be overcome before routine clinical applications are used. Currently, we are launching a novel class of RNAi therapeutic agents (PnkRNA™, nkRNA) that show high resistance to degradation and are less immunogenic, less cytotoxic, and capable of efficient intracellular delivery. Here, we develop a novel platform to promote naked RNAi approaches administered through inhalation without sophisticated delivery technology in mice. Furthermore, a naked and unmodified novel RNAi agent, such as ribophorin II (RPN2-PnkRNA), which has been selected as a therapeutic target for lung cancer, resulted in efficient inhibition of tumor growth without any significant toxicity. Thus, this new technology using aerosol delivery could represent a safe, potentially RNAi-based strategy for clinical applications in lung cancer treatment without delivery vehicles.

• Authors: Yu Fujita, Fumitaka Takeshita, Takayuki Mizutani, Tadaaki Ohgi, Kazuyoshi Kuwano, Takahiro Ochiya
• Journal: Scientific reports (Sci Rep) Vol. 3 Pg. 3325 (Nov 25 2013) ISSN: 2045-2322 [Electronic] England
• PMID: 24270189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cytokines
• Drug Carriers
• Nasal Sprays
• RNA, Small Interfering
• Luciferases
• Hexosyltransferases
• RPN2 protein, human
• Proteasome Endopeptidase Complex

Topics

• Adenocarcinoma (drug therapy, genetics)
• Adenocarcinoma of Lung
• Administration, Inhalation
• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cytokines (analysis)
• Drug Carriers (therapeutic use)
• Hexosyltransferases (genetics)
• Humans
• Luciferases (genetics)
• Lung (pathology)
• Lung Neoplasms (drug therapy, genetics)
• Male
• Mice
• Mice, SCID
• Nasal Sprays
• Neoplasm Transplantation
• Proteasome Endopeptidase Complex (genetics)
• RNA Interference
• RNA, Small Interfering (genetics, therapeutic use)
• Transplantation, Heterologous