Use of Sterically Stabilized Cationic Liposomes to Efficiently Deliver CpG Oligonucleotides in vivo
Description of Invention:
Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. This invention claims use of Sterically Stabilized Cationic Liposomes (SSCL) to deliver CpG ODNs. In addition to use of SSCL to deliver CpG ODNs, SSCL-CpG compositions are also claimed in the patent application. The claimed SSCL comprise three distinct phospholipid elements, DC-CHOL (which increases liposome membrane stability while improving the uptake and encapsulation of DNA), DOPE (a pH-sensitive neutral lipid that improves the cytosolic delivery of CpG ODNs following internalization), and PEG-PE (which stabilizes the liposome and also facilitates cellular uptake). The inventors have conducted both in vivo and in vitro studies using the SSCL-CpG compositions, showing that in vitro, liposome-encapsulated CpG ODNs stimulated significantly more interferon-gamma (IFN-gamma) production than free CpG ODNs. The in vivo testing the inventors completed show that SSCL encapsulation of CpG ODNs increases the magnitude and duration of the activity of the CpG ODNs in vivo; when CpG-SSCLs were administered to mice infected with L. monocytogenes (listeria), one hundred percent of the infected mice survived four weeks post-treatment.
Inventors:
Dennis Klinman (FDA) Ihsan Gursel (FDA)
Relevant Publication:
The invention is further described in Gursel I et al., "Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of cpg oligonucleotides," J. Immunol. 2001 Sep 15;167(6):3324-8.
For Additional Information Please Contact: Cristina Thalhammer-Reyero PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4507
Email: thalhamc@mail.nih.gov
Fax: (301) 402-0220
