mRNA delivery through fibronectin associated liposome-apatite particles: a new approach for enhanced mRNA transfection to mammalian cell.
It was believed for a long time that mRNA is very unstable, and can not be used for therapeutic purposes. In the last decade, however, many research groups proved its transfection feasibility along with advantages and applications. Our investigation is aimed at establishing a potent and efficient mRNA delivery system. We previously reported that an inorganic-organic hybrid carrier by exploiting the advantages of inorganic nano apatite particles onto organic carrier DOTAP {N-[1-(2,3-dioleoloxy)propyl]-N,N,N-trimethyl ammonium chloride} and showed potential effect of carbonate apatite particles on each of the mRNA delivery steps in dividing and non-dividing cell. Here, we report on the development of a more efficient mRNA carrier by complexing ECM protein, fibronectin with the DOTAP-apatite carrier. The carrier showed enhanced uptake of luciferase mRNA both qualitatively and quantitatively. Accelerated cellular endocytosis rate was evaluated using labeled endosome. Finally expression of lucifearse mRNA was higher for fibronectin complexed carrier in compared to the uncoated one.
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226–8501, Japan.
Fatema Tuj
FT
Zohra
Yoshie
Y
Maitani
Toshihiro
T
Akaike
D000818:Animals; D001031:Apatites; D004337:Drug Carriers; D004705:Endocytosis; D005229:Fatty Acids, Monounsaturated; D005353:Fibronectins; D015316:Genetic Therapy; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008322:Mammals; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000627:therapeutic use; D014162:Transfection / Q000379:methods*
D001031:Apatites; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D005353:Fibronectins; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D008156:Luciferases; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane