Magnetic nanoparticles with surface modification enhanced gene delivery of HVJ-E vector.
To enter the realm of human gene therapy, a novel drug delivery system is required for efficient delivery of small molecules with high safety for clinical usage. We have developed a unique vector "HVJ-E (hemagglutinating virus of Japan-envelope)" that can rapidly transfer plasmid DNA, oligonucleotide, and protein into cells by cell-fusion. In this study, we associated HVJ-E with magnetic nanoparticles, which can potentially enhance its transfection efficiency in the presence of a magnetic force. Magnetic nanoparticles, such as maghemite, with an average size of 29 nm, can be regulated by a magnetic force and basically consist of oxidized Fe which is commonly used as a supplement for the treatment of anemia. A mixture of magnetite particles with protamine sulfate, which gives a cationic surface charge on the maghemite particles, significantly enhanced the transfection efficiency in an in vitro cell culture system based on HVJ-E technology, resulting in a reduction in the required titer of HVJ. Addition of magnetic nanoparticles would enhance the association of HVJ-E with the cell membrane with a magnetic force. However, maghemite particles surface-coated with heparin, but not protamine sulfate, enhanced the transfection efficiency in the analysis of direct injection into the mouse liver in an in vivo model. The size and surface chemistry of magnetic particles could be tailored accordingly to meet specific demands of physical and biological characteristics. Overall, magnetic nanoparticles with different surface modifications can enhance HVJ-E-based gene transfer by modification of the size or charge, which could potentially help to overcome fundamental limitations to gene therapy in vivo.
Morishita
Norio
N
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Nakagami
Hironori
H
Morishita
Ryuichi
R
Takeda
Shin-ichi
S
Mishima
Fumihito
F
Terazono
Bungo
B
Nishijima
Shigehiro
S
Kaneda
Yasufumi
Y
Tanaka
Noriaki
N
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D008099:Liver / Q000166:cytology* / Q000821:virology*; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008846:Micromanipulation / Q000379:methods; D043942:Nanotubes / Q000737:chemistry*; D029082:Sendai virus / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014759:Viral Envelope Proteins / Q000235:genetics
D014759:Viral Envelope Proteins