Recombinant expression of human lipoprotein lipase in lower eukaryotes: preliminary results.

Familial Chylomicronemia Syndrome (FCS) is a very rare inherited disorder with extremely painful and severe, potentially fatal condition. Current therapies of FCS, like restriction of dietary fat or LipoProtein Lipase (LPL) gene therapy, have been only minimally effective [1,2]. LPL is a rate-limiting enzyme that catalyzes the hydrolysis of the TriGlyceride (TG) core of circulating TG-rich lipoproteins [3]. The development of an efficient expression system is a prerequisite for any future pharmacological application. We investigate the potential of a novel microbial factory based on lower eukaryotes for the recombinant expression of LPL aimed at achieving suitable amount of properly folded and active LPL. This achievement will pave the way at characterizing the structure of new LPL complexes (i.e. LMF1, GPIHBP1, APOC factors, Heparin). In our preliminary studies, we firstly employed filamentous fungi of Aspergillus genera as novel microbial platform and we tested the capability of, in particular, A. nidulans to express the human LPL in solution. Our achievements consist of the starting point for the system efficiency optimization. This approach is coupled to the localization of LPL in the mice hypothalamus, as the protein is involved in the cell energy balance [4]. [1] A.J. Braham, R.A. Hegele. Nat Rev Endocrinol 2015, 11:352–362. [2] L.M. Bryant, D.M. Christopher, A.R. Giles, C. Hinderer, J.L. Rodriguez, J.B. Smith, E.A. Traxler, J. Tycko, A.P. Wojno, J.M. Wilson. Hum Gene Ther Clin Dev 2013, 24:55-64. [3] J.R. Mead, S.A. Irvine, D.P. Ramji. J Mol Med (Berl) 2002, 80:753-769. [4] H. Wang, R.H. Eckel. Annu Rev Nutr 2012, 32:147-160.