Sol Fusin: Use of GP64-6HIS to Catalyze Membrane Fusion
Description of Invention:
An efficient drug delivery system is a necessity for a wide range of therapeutic interventions. This technology pertains to a process related to the solubilizing of insoluble membrane proteins, thus generating soluble and functional version (sol-proteins) of previously insoluble proteins. Specifically, the invention relates to the addition of histidine amino acids to the cytoplasmic domains of membrane and viral envelope proteins for the purpose of solubilizing, purifying and/or reconstituting functional viral envelope proteins in lipid-containing vesicles. The modified protein mediates fusion of the resulting vesicular membrane with other lipid membranes, thus creating an efficient delivery system. The proteins in this form have been referred to as 'sol-fusin' and the resultant sol-fusin/liposome complex is potentially able to catalyze delivery of therapeutic, genetic, or antigenic compounds both in vivo and in vitro. Thus, pharmaceutical and vaccine manufacturers may use these proteoliposomes as tools to deliver active therapeutic, genetic or antigenic agents without destruction by lysosomes. In addition to being useful as a delivery tool, the sol-fusin/ liposomes can be used to mimic viral infections. The triggering of sol-fusin is low pH-dependent, and thus may perhaps facilitate oral ingestion and gastrointestinal absorption of the bioactive agents because of their direct membrane fusion mediating activity.
Inventors:
David H. Kingsley and Joshua J. Zimmerberg (NICHD)
Patent Status:
DHHS Reference No. E-113-1999/0 --
U.S. Provisional Application No. 60/249,415 filed 15 Nov 2000
PCT Application No. PCT/US01/44909 filed 15 Nov 2001, which published as WO 02/40504 on 23 May 2002
U.S. Patent Application No. 10/416,979 filed 03 Oct 2003
Portfolios: Internal Medicine
Internal Medicine-Therapeutics
For Additional Information Please Contact: Sury Vepa PhD
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-5020
Email: vepas@mail.nih.gov
Fax: 301/402-0220
