Efficient Biodistribution and Gene Silencing in the Lung epithelium via Intravenous Liposomal Delivery of siRNA
نویسندگان
چکیده
RNA interference (RNAi) may provide a therapeutic solution to many pulmonary epithelium diseases. However, the main barrier to the clinical use of RNAi remains the lack of efficient delivery vectors. Research has mainly concentrated on the intranasal route of delivery of short interfering RNA (siRNA) effector molecules for the treatment of respiratory diseases. However, this may be complicated in a diseased state due to the increased fluid production and tissue remodeling. Therefore, we investigated our hydration of a freeze-dried matrix (HFDM) formulated liposomes for systemic delivery to the lung epithelium. Here, we show that 45 ± 2% of epithelial murine lung cells receive siRNA delivery upon intravenous (IV) liposomal administration. Furthermore, we demonstrate that liposomal siRNA delivery resulted in targeted gene and protein knockdown throughout the lung, including lung epithelium. Taken together, this is the first description of lung epithelial delivery via cationic liposomes, and provides a proof of concept for the use of IV liposomal RNAi delivery to specifically knockdown targeted genes in the respiratory system. This approach may provide an attractive alternate therapeutic delivery strategy for the treatment of lung epithelium diseases.Molecular Therapy - Nucleic Acids (2013) 2, e96; doi:10.1038/mtna.2013.22; published online 4 June 2013.
منابع مشابه
The Efficiency of CD40 Down Regulation by siRNA and Antisense ODN: Comparison of Lipofectamine and FuGENE6
Background: Dendritic cells (DCs) are ideal accessory cells in the field of gene therapy. Delivery of DNA and siRNA into mammalian cells is a useful technique in treating various diseases caused by single gene defects. Selective gene silencing by small interfering RNAs (siRNAs) and antisense oligodeoxynucleotides (ODN)s is an efficient method for the manipulation of cellular functions. An effic...
متن کاملTerpene-loaded liposomes and isopropyl myristate as chemical permeation enhancers toward liposomal gene delivery in lung cancer cells; A comparative study
Gene therapy is in its development stage as a novel method for cancer treatment. Liposomes look promising as gene delivery vectors; however, investigations have shown that these vesicles are not doing well in some cases. It was decided here to investigate the possibility of augmentation of liposomal gene delivery by chemical penetration enhancers.Cationic liposome containing antisense oligonucl...
متن کاملSmall interfering RNA; principles, applications and challenges--
Gene silencing using RNAi (RNA interference), has recently been used as a successful laboratory technique in determining the function and control of gene expression and provides a wide range of applications in molecular biology and gene therapy. RNAi is a method of suppressing gene expression. In this direction, a single-stranded RNA molecule of about 21–23 nucleotides, called siRNA (small inte...
متن کاملTerpene-loaded liposomes and isopropyl myristate as chemical permeation enhancers toward liposomal gene delivery in lung cancer cells; A comparative study
Gene therapy is in its development stage as a novel method for cancer treatment. Liposomes look promising as gene delivery vectors; however, investigations have shown that these vesicles are not doing well in some cases. It was decided here to investigate the possibility of augmentation of liposomal gene delivery by chemical penetration enhancers.Cationic liposome containing antisense oligonucl...
متن کاملFormulation of a therapeutic cationic liposome-siRNA complex for development to fight osteosarcoma
Introdution: Cationic liposomes have been presented for gene delivery as an alternative vector instead of viral vectors. A major challenge associated with siRNA delivery is the instability of liposomes, which is still a serious problem. The aim of this study was to provide an appropriate formulation to overcome this instability. Methods: In the present study (Scientific-Fundamental, Experiment...
متن کامل