Development of efficient packaging method of oligodeoxynucleotides by a condensed nano particle in lipid envelope structure.

An efficient delivery system is required if antisense oligodeoxynucleotides (ODN) are to be utilized for gene therapy. We report herein on the development of a novel ODN delivery system, ODN-encapsulated nano particles (ODN-ENP) using an efficient and simple packaging method. The ODN-ENP consists of a condensed ODN particle and a lipid envelope, which can be equipped with various functional devices for the efficient delivery of ODN with a small diameter (150 nm). The encapsulation efficiency and ODN recovery of ODN-ENP were significantly higher than those of other packaging methods, such as a stabilized antisense-lipid particles method or a freeze-thaw method. Furthermore, the time required for the preparation of the ODN-ENP was shorter than the other methods. The method developed in this study is a simple and efficient packaging method for ODN with a condensed nano particle in lipid-envelope structure.

[1]  F. Pastorino,et al.  Targeted Delivery of Oncogene‐Selective Antisense Oligonucleotides in Neuroectodermal Tumors: Therapeutic Implications , 2004, Annals of the New York Academy of Sciences.

[2]  P. Cullis,et al.  Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures. , 2001, Biochimica et biophysica acta.

[3]  Chi-Fang Chang,et al.  Inhibition of simian virus 40 large tumor antigen expression in human fetal glial cells by an antisense oligodeoxynucleotide delivered by the JC virus-like particle. , 2004, Human gene therapy.

[4]  M. Gleave,et al.  Synergistic antitumor effect of combined use of adenoviral-mediated p53 gene transfer and antisense oligodeoxynucleotide targeting clusterin gene in an androgen-independent human prostate cancer model. , 2005, Molecular cancer therapeutics.

[5]  Hideyoshi Harashima,et al.  Pharmacokinetic and pharmacodynamic considerations in gene therapy. , 2003, Drug discovery today.

[6]  D. Hoekstra,et al.  Effective intracellular delivery of oligonucleotides in order to make sense of antisense. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[7]  B. McManus,et al.  A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts , 2004, Laboratory Investigation.

[8]  D. Stuart,et al.  A novel, long-circulating, and functional liposomal formulation of antisense oligodeoxynucleotides targeted against MDR1 , 2000, Cancer Gene Therapy.

[9]  H Harashima,et al.  Mechanism of improved gene transfer by the N-terminal stearylation of octaarginine: enhanced cellular association by hydrophobic core formation , 2004, Gene Therapy.

[10]  M. Chevallier,et al.  Inhibition of hepadnaviral replication by polyethylenimine-based intravenous delivery of antisense phosphodiester oligodeoxynucleotides to the liver , 2001, Gene Therapy.

[11]  H Harashima,et al.  Stearylated arginine-rich peptides: a new class of transfection systems. , 2001, Bioconjugate chemistry.

[12]  T. Abe,et al.  Inhibition of HIV-1 replication by a new type of circular dumbbell RNA/DNA chimeric oligonucleotides. , 2000, Biochemical and biophysical research communications.

[13]  T. Allen,et al.  Targeted delivery system for antisense oligonucleotides: a novel experimental strategy for neuroblastoma treatment. , 2003, Cancer letters.

[14]  Shiroh Futaki,et al.  Development of a non-viral multifunctional envelope-type nano device by a novel lipid film hydration method. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[15]  Kazuo Maruyama,et al.  Transferrin-modified liposomes equipped with a pH-sensitive fusogenic peptide: an artificial viral-like delivery system. , 2004, Biochemistry.