Compositions and methods utilizing lysophosphatidylcholine scaffolds

Abstract

The invention relates to compositions and methods for utilizing lysophosphatidylcholine scaffolds. The compositions and methods can be used for LPC-mediated delivery of fatty acids and other molecules; to screen and identify fatty acid formulations for parenteral nutrition; and for live animal organ imaging, among other uses. The invention also provides compositions and methods for utilizing mutations and polymorphisms in human Mfsd2a as markers for neurological deficits.

1 . A method for screening one or more compound to determine transport via the Mfsd2a protein, the method comprising:
 (a) contacting a biological mixture comprising said one or more compound with a genetically modified mouse that comprises in its genome a homozygous disruption of the Mfsd2a gene (KO mouse) and a wild type mouse;   (b) measuring the amount of said one or more compound in a tissue or fluid of the KO mouse and the wild type mouse; and   (c) comparing the amount of said one or more compound in the tissue or fluid of the KO mouse and the wild-type mouse, wherein higher amounts of said one or more compound in the wildtype mouse as compared to the KO mouse is an indication of transport of the compound via Mfsd2a protein.   
     
     
         2 . The method of  claim 1 , wherein the KO mouse does not express functional Mfsd2a protein. 
     
     
         3 . The method of  claim 1 , wherein the biological mixture is derived from milk, fish oil extracts, or LPC formulations. 
     
     
         4 . The method of  claim 1 , wherein the tissue or fluid is brain, eye, liver, heart, or breast milk. 
     
     
         5 . A method of  claim 1 , wherein the method of contacting is via oral or i.v. administration. 
     
     
         6 . A method of  claim 1 , wherein said one or more compound is a nutritional supplement. 
     
     
         7 . A method of  claim 6 , wherein the nutritional supplement is a LPC formulation. 
     
     
         8 .- 10 . (canceled) 
     
     
         11 . A nutritional supplement comprising one or more LPC components selected from the group consisting of: LPC-16:0, LPC-18:0, LPC-18:1, LPC-18:2 n-6, LPC-20:4 n-6, LPC-22:6 n-3, and LPC-20:5 n-3. 
     
     
         12 . The nutritional supplement of  claim 11 , comprising LPC-16:0, LPC-18:0, LPC-18:1, LPC-18:2 n-6, LPC-20:4 n-6, LPC-22:6 n-3, and LPC-20:5 n-3 at the concentrations of 37, 14, 10, 20, 4, 25, and 0.5 mM respectively. 
     
     
         13 . The nutritional supplement of  claim 11  further comprising human albumin or an additional lipid formula selected from the group consisting oflntralipid™, SMOFKabiven™, Omegaven™, Lipofundin™, ClinOleic™, and Liposyn™. 
     
     
         14 .- 33 . (canceled) 
     
     
         34 . A composition comprising a scaffold conjugated to a compound. 
     
     
         35 . The composition of  claim 34 , wherein the scaffold is LPC. 
     
     
         36 . The composition of  claim 35 , wherein the compound is conjugated to LPC via the omega carbon of LPC. 
     
     
         37 . The composition of  claim 34 , wherein the compound is a pharmaceutical agent. 
     
     
         38 . The composition of  claim 34 , wherein the compound is an imaging agent. 
     
     
         39 .- 57 . (canceled) 
     
     
         58 . The composition of  claim 35 , wherein the scaffold comprises a zwitterionic head group and an acyl or alkyl chain.